250 results on '"α1 adrenergic receptor"'
Search Results
2. α1-adrenoceptor stimulation ameliorates lipopolysaccharide-induced lung injury by inhibiting alveolar macrophage inflammatory responses through NF-κB and ERK1/2 pathway in ARDS
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Zhukai Cong, Cui Yang, Zhaojin Zeng, Changyi Wu, Feng Zhao, Ziyuan Shen, Han Xiao, and Xi Zhu
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acute respiratory distress syndrome ,α1 adrenergic receptor ,alveolar macrophage ,inflammation ,NF-κb ,Immunologic diseases. Allergy ,RC581-607 - Abstract
IntroductionCatecholamines such as norepinephrine or epinephrine have been reported to participate in the development of acute respiratory distress syndrome (ARDS) by activating adrenergic receptors (ARs). But the role of α1-AR in this process has yet to be elucidated.MethodsIn this study, ARDS mouse model was induced by intratracheal instillation of lipopolysaccharide. After treatment with α1-AR agonist phenylephrine or antagonist prazosin, lung pathological injury, alveolar barrier disruption and inflammation, and haemodynamic changes were evaluated. Cytokine levels and cell viability of alveolar macrophages were measured in vitro. Nuclear factor κB (NF-κB), mitogen-activated protein kinase, and Akt signalling pathways were analysed by western blot.ResultsIt showed that α1-AR activation alleviated lung injuries, including reduced histopathological damage, cytokine expression, and inflammatory cell infiltration, and improved alveolar capillary barrier integrity of ARDS mice without influencing cardiovascular haemodynamics. In vitro experiments suggested that α1-AR stimulation inhibited secretion of TNF-α, IL-6, CXCL2/MIP-2, and promoted IL-10 secretion, but did not affect cell viability. Moreover, α1-AR stimulation inhibited NF-κB and enhanced ERK1/2 activation without significantly influencing p38, JNK, or Akt activation.DiscussionOur studies reveal that α1-AR stimulation could ameliorate lipopolysaccharide-induced lung injury by inhibiting NF-κB and promoting ERK1/2 to suppress excessive inflammatory responses of alveolar macrophages.
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- 2023
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3. α1-Adrenergic receptor mediates adipose-derived stem cell sheet-induced protection against chronic heart failure after myocardial infarction in rats
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Horie, Hiromu, Hisatome, Ichiro, Kurata, Yasutaka, Yamamoto, Yasutaka, Notsu, Tomomi, Adachi, Maaya, Li, Peili, Kuwabara, Masanari, Sakaguchi, Takuki, Kinugasa, Yoshiharu, Miake, Junichiro, Koba, Satoshi, Tsuneto, Motokazu, Shirayoshi, Yasuaki, Ninomiya, Haruaki, Ito, Shin, Kitakaze, Masafumi, Yamamoto, Kazuhiro, Yoshikawa, Yasushi, and Nishimura, Motonobu
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- 2022
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4. α1 adrenergic receptors in serum and saliva of patients with oral squamous cell carcinoma
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Amir-Hossein Mohebbi, Nafiseh Sheykhbahaei, Narges Gholizadeh, and Iraj Mirzaii-Dizgah
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Adult ,Male ,0301 basic medicine ,Cancer Research ,Sympathetic nervous system ,Saliva ,medicine.medical_specialty ,Adrenergic receptor ,Adrenergic ,α1 adrenergic receptor ,03 medical and health sciences ,0302 clinical medicine ,Receptors, Adrenergic, alpha-1 ,Internal medicine ,medicine ,Carcinoma ,Humans ,Basal cell ,Receptor ,Aged ,Aged, 80 and over ,Squamous Cell Carcinoma of Head and Neck ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,stomatognathic diseases ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Oncology ,Head and Neck Neoplasms ,Case-Control Studies ,030220 oncology & carcinogenesis ,Female ,business - Abstract
Neurotransmitters released from the sympathetic nervous system attach to the adrenergic receptors on the surface of tumoral cells in response to stress, and alter the expression of genes programming cellular activity. This study aimed to assess the expression of α1 adrenergic receptors in the serum and saliva of patients with oral squamous cell carcinoma (OSCC) compared with healthy controls. In this case–control study, serum and stimulated and unstimulated saliva samples were collected from 26 OSCC patients and 26 healthy controls. ELISA kits were used for measurement of the serum and salivary levels of α1 adrenergic receptors. The level of α1 adrenergic receptors was significantly higher in the stimulated and unstimulated saliva of OSCC patients than healthy controls (P = 0.000). However, their serum level was not significantly different between the two groups (P = 0.389). The serum level of α1 adrenergic receptors significantly increased by an increase in OSCC grade. No significant correlation was noted between the serum and salivary levels of α1 adrenergic receptors in OSCC patients. The salivary level of α1 adrenergic receptors was significantly higher in patients with tumors located in the gingiva, compared with other sites. Significantly higher salivary level of α1 adrenergic receptors in OSCC patients compared with healthy controls, and no significant difference in their serum level between the two groups may indirectly indicate the over-expression of these receptors in OSCC cells, compared with normal oral mucosa. Further studies and particularly histological analyses are required to confirm this finding.
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- 2021
5. Doxazosin attenuates renal matrix remodeling mediated by anti-α1-adrenergic receptor antibody in a rat model of diabetes mellitus.
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LIN-SHUANG ZHAO, YAN-YAN LIN, YI LIU, CHUN-YAN XU, YE LIU, WEI-WEI BAI, XUE-YING TAN, DE-ZHONG LI, and JIN-LING XU
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DIABETIC nephropathies , *DIABETES , *ADRENERGIC receptors , *DOXAZOSIN , *ELECTRON microscopy - Abstract
Diabetic nephropathy is a major complication of diabetes mellitus (DM). Recent studies suggest that immunological mechanisms have a key role in the pathogenesis of DM, therefore these mechanisms may be important targets for diabetes therapy. The present study evaluated the effects of anti-α1-adrenergic receptor antibody (α1-R Ab) mediation and doxazosin treatment in a rat model of DM. It was observed that levels of 24-h urinary protein, serum creatinine and transforming growth factor-β1 in DM were significantly increased after α1-R Ab mediation (all P<0.05). In addition, electron microscopy identified severe damage in the renal tissue microstructures of DM rats following α1-R Ab mediation, while only mild abnormalities were observed in that of healthy rats mediated with α1-R Ab and of untreated DM rats. No marked abnormalities were observed in the renal tissue of healthy blank controls. Furthermore, in DM rats treated with α1-R Ab mediation + doxazosin intervention, the expression of TGF-β1 significantly decreased, and renal functions and renal matrix remodeling were significantly improved, relative to untreated DM controls (P<0.01). These results suggest that α1-R Ab may be involved in renal matrix remodeling during DM, and that kidney protection during DM may be achieved through treatment with corresponding receptor antagonists. [ABSTRACT FROM AUTHOR]
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- 2017
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6. Upregulations of α1 adrenergic receptors and noradrenaline synthases in the medial prefrontal cortex are associated with emotional and cognitive dysregulation induced by post-weaning social isolation in male rats.
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Kawanabe, Shunsuke, Mori, Masayoshi, Harada, Hiroyoshi, Murata, Yusuke, Ohe, Kenji, and Enjoji, Munechika
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ADRENERGIC receptors , *SOCIAL isolation , *PREFRONTAL cortex , *NORADRENALINE , *SYNTHASES , *DESPAIR , *LONELINESS - Abstract
• Male rats were subjected to post-weaning social isolation for 9 weeks. • Social isolation induced cognitive dysfunction, anxiety, and aggression. • Social isolation increased the levels of α 1 adrenergic receptor protein in the mPFC. Early-life social isolation induces emotional and cognitive dysregulation, such as increased aggression and anxiety, and decreases neuron excitability in the medial prefrontal cortex (mPFC). The noradrenergic system in the mPFC regulates emotion and cognitive function via α 1 or α 2A adrenergic receptors, depending on noradrenaline levels. However, social isolation-induced changes in the mPFC noradrenergic system have not been reported. Here, male Wistar rats received post-weaning social isolation for nine consecutive weeks and were administered behavioral tests (novel object recognition, elevated plus maze, aggression, and forced swimming, sequentially). Protein expression levels in the mPFC noradrenergic system (α 1 and α 2A adrenergic receptors, tyrosine hydroxylase, and dopamine-β-hydroxylase used as indices of noradrenaline synthesis and release) were examined through western blotting. Social isolation caused cognitive dysfunction, anxiety-like behavior, and aggression, but not behavioral despair. Socially-isolated rats exhibited increased protein levels of the α 1 adrenergic receptor, tyrosine hydroxylase, and dopamine-β-hydroxylase in the mPFC; there was no significant difference between the groups in the α 2A adrenergic receptor expression levels. Preferential activation of the α 1 adrenergic receptor caused by high noradrenaline concentration in the mPFC may be involved in social isolation-induced emotional and cognitive regulation impairments. Targeting the α 1 adrenergic receptor signaling pathway is a potential therapeutic strategy for psychiatric disorders with symptomatic features such as emotional and cognitive dysregulation. [ABSTRACT FROM AUTHOR]
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- 2023
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7. α1-Adrenergic receptors increase glucose oxidation under normal and ischemic conditions in adult mouse cardiomyocytes
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Dianne M. Perez and Robert S. Papay
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0301 basic medicine ,medicine.medical_specialty ,Chemistry ,Energy metabolism ,Cell Biology ,Metabolism ,Biochemistry ,α1 adrenergic receptor ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Endocrinology ,030220 oncology & carcinogenesis ,Internal medicine ,cardiovascular system ,medicine ,Catecholamine ,Whole body ,Receptor ,Molecular Biology ,medicine.drug ,G protein-coupled receptor - Abstract
The role of catecholamine receptors in cardiac energy metabolism is unknown. α1-adrenergic receptors (α1-ARs) have been identified to play a role in whole body metabolism but its role in cardiac en...
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- 2020
8. Inhibiting α1-adrenergic Receptor Signaling Pathway Ameliorates Alzheimer’s Disease Type Pathologies and Behavioral Deficits in an AD Mouse Model
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Yuan Cheng, Pu-Yang Sun, Zhong-Yuan Yu, Yan-Jiang Wang, Yu-Hui Liu, Zhi-Hao Liu, Xu Yi, Gui-Hua Zeng, Ye-Ran Wang, and Cheng-Rong Tan
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nervous system ,business.industry ,Medicine ,Disease ,Signal transduction ,business ,α1 adrenergic receptor ,Neuroscience - Abstract
Background The role of α1 adrenergic receptors (α1-ARs) signaling pathway in the pathogenesis of Alzheimer’s disease (AD) has rarely been investigated. Clarifying pathophysiological functions of α1-ARs in the AD brain is helpful for better understanding the pathogenesis and screening novel therapeutic target of AD. Methods This study included 2 arms of in vivo investigations: 1) 6-month-old female APPswe/PS1 mice were intravenously treated with AAV-PHP.eB-shRNA (ARs)-GFP or AAV-PHP.eB-GFP for 3 months. 2) 3-month-old female APPswe/PS1 mice were daily treated with 0.5 mg/kg terazosin or equal saline for 6 months. SH-SY5Y cell lines bearing human Amyloid precurssor protein were treated with terazosin or saline for investigating possible mechanisms. Results α1-ARs knockdown mice exhibited improved behavioral performances than control mice. α1-ARs knockdown mice had significantly lower brain amyloid burden, as reflected by soluble Aβ species, compact and total plaques, than control mice. The α1-ARs inhibitor terazosin substantially reduced Aβ deposition, attenuated downstream pathologies including Tau hyperphosphorylation, glial activation, neuronal loss, synaptic dysfunction, and rescued behavioral deficits of APPswe/PS1 mice. In vitro investigation demonstrated that α1-ARs inhibition down-regulated BACE1 expression, and promoted ser9 phosphorylation of GSK-3β, thus reduced Aβ production. Conclusions This study indicates that inhibition of α1-ARs signaling pathway might represent a promising therapeutic strategy for AD.
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- 2021
9. α 1 -adrenoceptor stimulation ameliorates lipopolysaccharide-induced lung injury by inhibiting alveolar macrophage inflammatory responses through NF-κB and ERK1/2 pathway in ARDS.
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Cong Z, Yang C, Zeng Z, Wu C, Zhao F, Shen Z, Xiao H, and Zhu X
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- Mice, Animals, NF-kappa B metabolism, Macrophages, Alveolar metabolism, MAP Kinase Signaling System, Lipopolysaccharides toxicity, Lipopolysaccharides metabolism, Proto-Oncogene Proteins c-akt metabolism, Cytokines metabolism, Receptors, Adrenergic metabolism, Lung Injury chemically induced, Respiratory Distress Syndrome metabolism
- Abstract
Introduction: Catecholamines such as norepinephrine or epinephrine have been reported to participate in the development of acute respiratory distress syndrome (ARDS) by activating adrenergic receptors (ARs). But the role of α1-AR in this process has yet to be elucidated., Methods: In this study, ARDS mouse model was induced by intratracheal instillation of lipopolysaccharide. After treatment with α1-AR agonist phenylephrine or antagonist prazosin, lung pathological injury, alveolar barrier disruption and inflammation, and haemodynamic changes were evaluated. Cytokine levels and cell viability of alveolar macrophages were measured in vitro. Nuclear factor κB (NF-κB), mitogen-activated protein kinase, and Akt signalling pathways were analysed by western blot., Results: It showed that α1-AR activation alleviated lung injuries, including reduced histopathological damage, cytokine expression, and inflammatory cell infiltration, and improved alveolar capillary barrier integrity of ARDS mice without influencing cardiovascular haemodynamics. In vitro experiments suggested that α1-AR stimulation inhibited secretion of TNF-α, IL-6, CXCL2/MIP-2, and promoted IL-10 secretion, but did not affect cell viability. Moreover, α1-AR stimulation inhibited NF-κB and enhanced ERK1/2 activation without significantly influencing p38, JNK, or Akt activation., Discussion: Our studies reveal that α1-AR stimulation could ameliorate lipopolysaccharide-induced lung injury by inhibiting NF-κB and promoting ERK1/2 to suppress excessive inflammatory responses of alveolar macrophages., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cong, Yang, Zeng, Wu, Zhao, Shen, Xiao and Zhu.)
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- 2023
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10. Effect of prazosin on diabetic nephropathy patients with positive α1-adrenergic receptor autoantibodies and refractory hypertension.
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LIN-SHUANG ZHAO and CHUN-YAN XU
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PRAZOSIN , *DIABETIC nephropathies , *HYPERTENSION , *AUTOANTIBODIES , *ENZYME-linked immunosorbent assay - Abstract
To investigate the effect of prazosin on patients with diabetic nephropathy (DN), α1-adrenergic receptor (α1-R) autoantibodies and refractory hypertension, a total of 126 patients with DN and hypertension were recruited. The patients were divided into a refractory hypertension group, (n=76) and a non-refractory hypertension group (n=50). The epitope of the second extracellular loop of the α1-R (192-218) was synthesized and an enzyme-linked immunosorbent assay (ELISA) was performed to detect serum autoantibodies. In the group with DN-associated refractory hypertension, the positive rate of autoantibodies against the α1-R was 80.3% (n=61). The 61 patients who were positive for α1-R autoantibodies were randomly divided into a treatment group (n=31) and a control group (n=30). The patients were given drugs at the same dosage and administration, with the exception of prazosin, which was provided only to the patients in the treatment group [1 mg, three times a day (tid)] for a duration of six weeks. Subsequently, prazosin was added (1 mg, tid) to the therapeutic schedule of the patients in the control group and the α1-R autoantibody-negative group for another six weeks. The analysis was carried out on an intention-to-treat basis. The prazosin treatment resulted in significant improvements in hypertension in the treatment group (P<0.05), while there was no marked improvement in the control group. The total effective rate of hypertension improvement was 90.3% in the treatment group, which was higher compared with that of the control group (33.3%). In conclusion, α1-R autoantibodies may play an important role in the pathogenesis of DN with refractory hypertension. Prazosin was demonstrated to be effective and safe in the treatment of DN with refractory hypertension. [ABSTRACT FROM AUTHOR]
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- 2015
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11. Increased vascular α1-adrenergic receptor sensitivity in older adults with posttraumatic stress disorder
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Yingtian Hu, C. Michael Stein, Doree G Morison, Justin D. Sprick, Cortnie Hartwig, Jinhee Jeong, Jeanie Park, and Sachin Y. Paranjape
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Male ,Sympathetic nervous system ,medicine.medical_specialty ,Aging ,Sympathetic Nervous System ,Physiology ,Blood Pressure ,Disease ,030204 cardiovascular system & hematology ,α1 adrenergic receptor ,Stress Disorders, Post-Traumatic ,03 medical and health sciences ,Vascular reactivity ,Phenylephrine ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,Receptors, Adrenergic, alpha-1 ,Medicine ,Humans ,Risk factor ,Infusions, Intravenous ,Dose-Response Relationship, Drug ,business.industry ,Age Factors ,Middle Aged ,Posttraumatic stress ,medicine.anatomical_structure ,Blood pressure ,Vasoconstriction ,Case-Control Studies ,Stress disorders ,Cardiology ,Female ,Adrenergic alpha-1 Receptor Agonists ,business ,030217 neurology & neurosurgery ,Signal Transduction ,Research Article - Abstract
Posttraumatic stress disorder (PTSD) is an independent risk factor for the development of hypertension and cardiovascular disease. Patients with PTSD have heightened blood pressure and sympathetic nervous system reactivity; however, it is unclear if patients with PTSD have exaggerated vasoconstriction in response to sympathetic nerve activation that could also contribute to increased blood pressure reactivity. Therefore, we hypothesized that patients with PTSD have increased sensitivity of vascular α1-adrenergic receptors (α1ARs), the major mediators of vasoconstriction in response to release of norepinephrine at sympathetic nerve terminals. To assess vascular α1AR sensitivity, we measured the degree of venoconstriction in a dorsal hand vein in response to exponentially increasing doses of the selective α1AR agonist, phenylephrine (PE), in 9 patients with PTSD (age = 59 ± 2 yr) and 10 age-matched controls (age = 60 ± 1 yr). Individual dose-response curves were generated to determine the dose of PE that induces 50% of maximal venoconstriction (i.e., PE ED50) reflective of vascular α1AR sensitivity. In support of our hypothesis, PE ED50values were lower in PTSD compared with controls (245 ± 54 ng/min vs. 1,995 ± 459 ng/min, P = 0.012), indicating increased vascular α1AR sensitivity in PTSD. The PTSD group also had an increase in slope of rise in venoconstriction, indicative of an altered venoconstrictive reactivity to PE compared with controls (19.8% ± 1.2% vs. 15.1% ± 1.2%, P = 0.009). Heightened vascular α1AR sensitivity in PTSD may contribute to augmented vasoconstriction and blood pressure reactivity to sympathoexcitation and to increased cardiovascular disease risk in this patient population.
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- 2020
12. Quantitation of In Vitro α-1 Adrenergic Receptor Antagonist Binding Capacity to Biologic Melanin Using Tandem Mass Spectrometry.
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Gaynes, Jeffrey S., Micic, Cedomir, Gaynes, Bruce I., and Borgia, Jeffrey A.
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ALPHA adrenoceptors , *CARRIER proteins , *MELANINS , *TANDEM mass spectrometry , *RHODOPSIN , *CHLOROQUINE , *IN vitro studies - Abstract
Purpose: The purpose of this study was to develop methods to allow evaluation of the binding characteristics for a series of α1 antagonists to biologically-derived melanin. Methods: Fresh bovine globes were used to obtain iridai and choroid/retinal pigment epithelial (CRPE) derived melanin. Binding characteristics of chloroquine, tamsulosin and doxazosin were then evaluated in vitro using tandem mass spectroscopy. Results: Tandem mass spectrometry-based assays were developed for three α1 antagonists that provided linear assay ranges which spanned (minimally) 0.01-10 μg/mL, while exhibiting excellent inter-assay precision and accuracy. When applied to the evaluation of binding characteristics for iridai melanin, mean chloroquine and tamsulosin fractions were found to be 41.9 ± 14.2 pmoles mg-1 and 25.34 ± 6.186 pmoles mg-1, respectively. Mean iridai doxazosin binding was found to be 6.36 ±2.19 pmoles mg-1. Interestingly, mean levels of tamsulosin, but not doxazosin found bound to choroid/CRPE derived melanin approached that of chloroquine (27.91 μg/mL, 25.68 μg/mL and 5.94 μg/mL for chloroquine, tamsulosin and doxazosin, respectively). One way ANOVA for binding affinity for chloroquine, tamsulosin and doxazosin was statistically significant for both iridai and CRPE-derived melanin (p = 0.0012 and 0.0023), respectively. A Bonferroni post-hoc analysis demonstrated a statistically significant difference in the amount of binding between tamsulosin, doxazosin and chloroquine to iridai but not CRPE derived melanin (p <0.05). Conclusions: Tamsulosin appears to demonstrate melanin binding affinity which approaches chloroquine and exceeds doxazosin for both iridai and CRPE-derived bovine melanin. [ABSTRACT FROM AUTHOR]
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- 2013
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13. Norepinephrine modulates the zonally different hepatocyte proliferation through the regulation of transglutaminase activity.
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Ohtake, Yosuke, Kobayashi, Tomonori, Maruko, Akiko, Oh-ishi, Nao, Yamamoto, Fumihiko, Katoh, Shinsuke, and Ohkubo, Yasuhito
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EPIDERMAL growth factor , *DNA synthesis , *ADRENERGIC receptors , *NEUROTRANSMITTERS , *G proteins , *ENZYMES - Abstract
A neurotransmitter, norepinephrine (NE), amplifies the mitogenic effect of epidermal growth factor (EGF) in the liver by acting on the α1-adrenergic receptor coupled with G protein, Gαh. However, the molecular mechanism is not well understood, Gαh is known as a transglutaminase 2 (TG2), a cross-linking enzyme implicated in hepatocyte proliferation. We investigated the effect of NE on EGF-induced cell proliferation and TG2 activity using hepatocytes isolated in periportal and perivenous regions of the liver, which differ in proliferative capacity. Periportal hepatocytes (PPH) and perivenous hepatocytes (PVH) were isolated by the digitonin-collagenase perfusion technique. EGF or NE receptor binding was analyzed by Scatchard analysis. Changes in NE-induced DNA synthesis, EGF receptor (EGFR) dimerization and phosphorylation, and TG2 activity were measured. NE enhanced EGF-induced DNA synthesis, EGF-induced EGFR dimerization, and its phosphorylation in PVH but not in PPH. [³H]NE binding studies indicated that PVH was found to have a greater affinity and number of receptors than PPH. Furthermore, NE treatment decreased TG2 activity and increased phospholipase C activity in PVH although TG2 level showed no change. These results suggest that NE-induced amplification of EGF-induced DNA synthesis especially in PVH is caused by upregulation of EGFR activation through the switching of function from TG2 to Gαh. [ABSTRACT FROM AUTHOR]
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- 2010
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14. Dual regulation of heat-activated K+ channel in rat DRG neurons via α1 and β adrenergic receptors
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Yamamoto, Satoshi, Kanno, Takeshi, Yamada, Kosaku, Yasuda, Yoshiyuki, and Nishizaki, Tomoyuki
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POTASSIUM channels , *PHYSIOLOGICAL effects of heat , *AUTONOMIC ganglia , *NEURONS , *ADRENERGIC receptors , *PROTEIN kinase C , *ENZYME activation , *NORADRENALINE - Abstract
Abstract: Aims: The present study aimed at understanding regulation of heat-activated K+ channels expressed in DRG neurons. Main methods: Whole-cell patches were made from cultured rat dorsal root ganglion (DRG) neurons and heat-activated currents were monitored. Key findings: A temperature rise from 25 to 45 °C generated outward currents with the current/voltage relation revealing a reversal potential of approximately −90 mV, that are inhibited by the K+ channel blockers, Ba2+ and tetraethylammonium, indicating that heat activates K+ channels expressed in DRG neurons. Heat-activated K+ channel currents here was depressed by noradrenaline, and a similar effect was obtained with cirazoline, an agonist of α1 adrenergic receptors linked to Gq protein involving PKC activation, and isoproterenol, an agonist of β adrenergic receptors linked to Gs protein involving PKA activation, but not UK14304, an agonist of α2 adrenergic receptors linked to Gi protein. The noradrenaline action was prevented by GF109203X, a PKC inhibitor, or H-89, a PKA inhibitor, and a complete inhibition was obtained with co-treatment with GF109203X and H-89. PMA, a PKC activator, or forskolin, an activator of adenylate cyclase, on the other hand, reduced heat-activated outward currents and co-treatment with PMA and forskolin further attenuated the currents to an extent similar to that for noradrenaline. Significance: The results of the present study show that heat-activated K+ channel currents in DRG neurons are inhibited by both PKC and PKA as mediated via α1 and β adrenergic receptors, respectively. This may represent a new insight into regulation of thermosensation via a noradrenergic pathway. [Copyright &y& Elsevier]
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- 2009
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15. Doxazosin attenuates renal matrix remodeling mediated by anti-α1-adrenergic receptor antibody in a rat model of diabetes mellitus
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De‑Zhong Li, Yan‑Yan Lin, Xue‑Ying Tan, Wei‑Wei Bai, Lin‑Shuang Zhao, Ye Liu, Chun‑Yan Xu, Jin‑Ling Xu, and Yi Liu
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,doxazosin ,030204 cardiovascular system & hematology ,Diabetic nephropathy ,Pathogenesis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Immunology and Microbiology (miscellaneous) ,Diabetes mellitus ,Internal medicine ,medicine ,Doxazosin ,Receptor ,renal matrix remodeling ,Kidney ,Creatinine ,business.industry ,Autoantibody ,General Medicine ,Articles ,medicine.disease ,α1 adrenergic receptor ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,chemistry ,diabetes mellitus ,business ,autoantibody ,medicine.drug - Abstract
Diabetic nephropathy is a major complication of diabetes mellitus (DM). Recent studies suggest that immunological mechanisms have a key role in the pathogenesis of DM, therefore these mechanisms may be important targets for diabetes therapy. The present study evaluated the effects of anti-α1-adrenergic receptor antibody (α1-R Ab) mediation and doxazosin treatment in a rat model of DM. It was observed that levels of 24-h urinary protein, serum creatinine and transforming growth factor-β1 in DM were significantly increased after α1-R Ab mediation (all P
- Published
- 2017
16. Mechanism of α1-adrenergic receptor-induced increased contraction of rat mesenteric artery in aging and hypertension
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Peng-Yun Li, Yan Yang, Jing Wen, Jun Cheng, Xiaorong Zeng, Yuanqun Zhou, and Na Wang
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medicine.medical_specialty ,Endocrinology ,Contraction (grammar) ,medicine.anatomical_structure ,Chemistry ,Internal medicine ,medicine ,Cardiology and Cardiovascular Medicine ,Molecular Biology ,α1 adrenergic receptor ,Artery - Published
- 2020
17. Vaccine Targeted Alpha 1D-Adrenergic Receptor for Hypertension
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Shijun Yang, Yumiao Wei, Zihua Zhou, Yanzhao Zhou, Danyu Wu, Yajie Pan, Xiao Chen, Xin Liang, Yuhua Liao, Fen Chen, Chang Li, Xiaole Yan, Kai Zhang, and Zhihua Qiu
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0301 basic medicine ,Male ,China ,medicine.medical_treatment ,Down-Regulation ,Alpha1 adrenergic receptor ,030204 cardiovascular system & hematology ,Pharmacology ,Kidney Function Tests ,α1 adrenergic receptor ,Rats, Sprague-Dawley ,03 medical and health sciences ,Random Allocation ,0302 clinical medicine ,Rats, Inbred SHR ,Receptors, Adrenergic, alpha-1 ,Internal Medicine ,medicine ,Animals ,Molecular Targeted Therapy ,Alpha-1D adrenergic receptor ,Vaccines ,business.industry ,Biopsy, Needle ,Immunotherapy ,Immunohistochemistry ,Rats ,Disease Models, Animal ,030104 developmental biology ,NG-Nitroarginine Methyl Ester ,Hypertension ,business - Abstract
The α1-AR (α1 adrenergic receptor) blockers currently on the market cannot meet clinical needs because of low-selectivity for subtypes of α1-ARs, short half-life, and uncertain role in cardiovascular end point events. The study sought to find a vaccine specifically against α1D-AR (α1D-adrenergic receptor) for treating hypertension. A short peptide ADR-004 (cgiteeagy) belonging to α1D-AR was screened, and the ADRQβ-004 vaccine was produced and injected into spontaneously hypertensive rats model (including a short-term study, 10 weeks, and a long-term observation study, 39 weeks) and NG-nitro- l -arginine methyl ester + spontaneously hypertensive rats model (15 weeks). The antihypertensive effect and target organ protection of the ADRQβ-004 vaccine were carefully evaluated. The possible immune-mediated damage was detected in normal vaccinated Sprague Dawley rats. The ADR-004 peptide has perfect immunogenicity, and the ADRQβ-004 vaccine could induce strong antibody production. In the short-term study, the ADRQβ-004 vaccine averagely decreased the systolic blood pressure of spontaneously hypertensive rats up to 15 mm Hg and that of NG-nitro- l -arginine methyl ester+spontaneously hypertensive rats up to 29 mm Hg. In the long-term observation model, the antihypertensive effect of the ADRQβ-004 vaccine was quite stable, and the average decline of systolic blood pressure was 22 mm Hg. The ADRQβ-004 vaccine effectively prevented vascular structural remodeling, cardiac hypertrophy and fibrosis, and renal injury of hypertensive animals, superior to prazosin at renal level. Moreover, the ADRQβ-004 vaccine obviously downregulated the expression of α1D-AR, but not α1A-AR. Additionally, no significant immune-mediated damage was detected in immunized animals. The present results demonstrate that the ADRQβ-004 vaccine may provide a novel and promising method for the treatment of hypertension.
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- 2019
18. SAT-037 Functional Interplay between Distinct P-TEFb Complexes Following Endothelin or α1-Adrenergic Receptor Activation in Rat Cardiomyocytes
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Ryan D. Martin, Terence E. Hébert, and Jason C. Tanny
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Chemistry ,Non-Steroid Hormone Signaling ,Endocrinology, Diabetes and Metabolism ,Endothelin receptor ,P-TEFb ,α1 adrenergic receptor ,Cell biology - Abstract
Heart disease is characterized by the remodelling of cardiac tissue following prolonged stress on the heart, such as myocardial infarction and chronic hypertension. The heart initially undergoes hypertrophy of the individual contractile unit, the cardiomyocyte, in order to preserve cardiac function. However, prolonged stress can lead to fibrosis, cardiomyocyte death, and subsequent heart failure. Cardiac remodelling is mediated predominantly through neurohormonal activation of G protein-coupled receptors (GPCRs) expressed by cardiomyocytes and other cell types in the heart. Current therapeutic approaches target implicated GPCRs to slow disease progression by inhibiting signalling pathways leading to remodelling. While this approach benefits a portion of patients, other therapeutic approaches are required to improve disease prognosis (1). A potential target downstream of GPCR activation is the transcription regulator positive transcription elongation factor b (P-TEFb). Hormonal activation of multiple GPCRs, such as the α1-adrenergic receptor (α1AR) by epinephrine or the endothelin receptor (ETR) by endothelin-1, leads to P-TEFb-dependent cardiomyocyte hypertrophy, a hallmark of cardiac remodelling (2). Active P-TEFb is recruited to chromatin to regulate gene expression as a constituent of two complexes, either through interactions with the Super Elongation Complex (SEC) or the bromodomain and extra-terminal protein Brd4. Small molecule inhibition of Brd4 prevents hypertrophy and activation of inflammatory and profibrotic genes in cardiomyocytes (3). On the other hand, the role of the SEC in regulating cardiomyocyte gene expression has not been examined. Furthermore, the signalling mechanisms leading to activation of either complex and subsequent gene expression changes are not known. We hypothesized that activation and interplay between distinct P-TEFb complexes differs following activation of different GPCRs implicated in heart failure. We assessed the role of Brd4 and the SEC downstream of the endogenous ETR and α1AR stimulated with endothelin-1 or phenylephrine, respectively, in primary neonatal rat cardiomyocytes. Although P-TEFb activity is required downstream of both receptors to drive gene expression changes and cardiomyocyte hypertrophy, we find evidence for receptor-specific differences in the functions of the SEC and the Brd4 complex. We are currently investigating signalling mechanisms regulating each complex downstream of the ETR and α1AR. Understanding how mechanisms downstream of various hormones differentially regulate transcription has clinical implications as therapies targeting transcriptional machinery are being explored for heart failure. (1) Wang et al., Circ Res. 2018; 123:716-35 (2) Sano et al., Nat Med. 2002; 8:1310-7 (3) Duan et al., Sci Transl Med; 9(390)
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- 2019
19. Discovery of Fluorescence Polarization Probe for the ELISA-Based Antagonist Screening of α1-Adrenergic Receptors
- Author
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Tianchao Zhang, Zhao Ma, Tianyu Jiang, Huateng Zhang, Lupei Du, Zhenzhen Liu, and Minyong Li
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0301 basic medicine ,Stereochemistry ,Chemistry ,Organic Chemistry ,Antagonist ,Ligand (biochemistry) ,Biochemistry ,α1 adrenergic receptor ,Fluorescence ,03 medical and health sciences ,Fluorescence intensity ,030104 developmental biology ,Drug Discovery ,Biophysics ,Receptor ,Fluorescence anisotropy ,G protein-coupled receptor - Abstract
High-throughput screening (HTS) of ligand library to find new active molecules for G protein-coupled receptors is still a major interest, as well as an actual challenge. Fluorescence polarization (FP) assay portrays an essential role in HTS; however, in many cases, it was restricted by the absence of FP probes, the narrow measurement window, and low signal-to-noise (S/N) ratio. Herein, based on the modification of our previous probe 1 (QFL), we discovered an FP probe 3 (QGGFL) for α1-adrenergic receptors (α1-ARs), which has satisfactory fluorescence intensity, specific binding ability to receptors, and suitable fluorescence properties that were compatible with the filters in the FP system. Meanwhile, an “ELISA-like” strategy was designed for FP-based HTS assay in which proteins were adhered into a solid phase to improve the measurement window and S/N ratio. With fluorescent antagonist QGGFL and the ELISA strategy, we succeeded in establishing the first competitive binding FP assay for α1-AR antagonists as...
- Published
- 2016
20. DHHC21‐mediated α1 Adrenergic Receptor Palmitoylation Contributes to Renal Blood Flow Regulation During Sepsis
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Ethan Zheng, Alexandria Creasy, Yonggang Ma, Jonathan W. Overstreet, Xiaoyuan Yang, Victor Chatterjee, and Sarah Y. Yuan
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Sepsis ,Palmitoylation ,business.industry ,Renal blood flow ,Genetics ,medicine ,Pharmacology ,medicine.disease ,business ,Molecular Biology ,Biochemistry ,α1 adrenergic receptor ,Biotechnology - Published
- 2020
21. Phosphatidic acid increases in response to noradrenaline and endothelin-1 in adult rabbit ventricular myocytes.
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Ye, Hongping, Wolf, Robert A, Kurz, Thomas, and Corr, Peter B
- Abstract
Objective: The aim was to assess whether noradrenaline and endothelin-1 can stimulate endogenous production of phosphatidic acid in adult ventricular myocytes. Methods: After stimulation of rabbit ventricular myocytes with noradrenaline and endothelin-1, total lipids were extracted using the Bligh and Dyer procedure and separated by thin layer chromatography, and phosphatidic acid was quantified using photodensitometric analysis of visualised lipids with CuSO4/H3PO4. Results: Noradrenaline (10−5 M) elicited a rapid increase in phosphatidic acid at 2 min, followed by a decrease at 5 min. A second delayed and sustained increase in phosphatidic acid occurred at 10 min. The response to noradrenaline (10−9 to 10−5 M) was concentration dependent with a half maximum response (EC50) of 3.1 × 10−8 M and the maximum effect at 10−6 M. The increase in phosphatidic acid production in response to noradrenaline was abolished by an α1 adrenergic receptor blocking agent (2-[β-(4-hydroxyphenyl)-ethylaminomethyl]tetralone) but unaffected by the β adrenergic blocking agent L-propranolol. An increase in phosphatidic acid was also elicited in rabbit ventricular myocytes in response to endothelin-1. The response was time and concentration dependent with the maximal increase at 12 min, EC50 5.3 × 10−9 M, and maximum effect at 10−6 M. Both noradrenaline and endothelin-1 stimulated phosphatidyl- butanol production in the presence of butanol (100 mM), indicating that both agonists activate phospholipase D. Conclusions: Noradrenaline at physiological concentrations elicits both a rapid and a delayed increase in phosphatidic acid in adult rabbit ventricular myocytes. Endothelial-1, at physiological concentrations, also stimulates an increase in the mass of phosphatidic acid in myocytes, but the increase induced by endothelin-1 is monophasic, in contrast to the biphasic response seen during stimulation with noradrenaline. Activation of phospholipase D contributes to the increase in phosphatidic acid seen during stimulation of myocytes with either noradrenaline or endothelin-1. These are the first data to characterise endogenous production of phosphatidic acid in isolated adult ventricular myocytes.Cardiovascular Research 1994;28:1828-1834 [ABSTRACT FROM PUBLISHER]
- Published
- 1994
22. α 1 ‐Adrenergic Receptors Function Within Hetero‐Oligomeric Complexes With Atypical Chemokine Receptor 3 and Chemokine (C‐X‐C motif) Receptor 4 in Vascular Smooth Muscle Cells
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Lauren J. Albee, Abhishek Tripathi, Matthias Majetschak, Heather M. LaPorte, Jonathan M. Eby, Brian F. Volkman, Vadim Gaponenko, and Xianlong Gao
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0301 basic medicine ,Chemokine ,Vascular smooth muscle ,Ligands ,Vascular Medicine ,Muscle, Smooth, Vascular ,Chemokine receptor ,Adenosine Triphosphate ,vasoconstriction ,Receptor ,Original Research ,adrenergic receptor ,biology ,blood pressure ,C‐X‐C motif chemokine ligand 11 ,C‐X‐C motif chemokine ligand 12 ,Cell biology ,RNA Interference ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Protein Binding ,Signal Transduction ,medicine.drug ,Receptors, CXCR4 ,alpha ,Adrenergic receptor ,Myocytes, Smooth Muscle ,Transfection ,α1 adrenergic receptor ,03 medical and health sciences ,Vascular Biology ,Receptors, Adrenergic, alpha-1 ,medicine ,Humans ,Protein Interaction Domains and Motifs ,Phenylephrine ,Receptors, CXCR ,Dose-Response Relationship, Drug ,business.industry ,chemokine ,Receptor Cross-Talk ,phenylephrine ,HEK293 Cells ,030104 developmental biology ,Multiprotein Complexes ,Immunology ,biology.protein ,Adrenergic alpha-1 Receptor Agonists ,business ,Basic Science Research ,Cell Signalling/Signal Transduction ,Vasoconstriction - Abstract
Background Recently, we provided evidence that α 1 ‐adrenergic receptors ( ARs ) in vascular smooth muscle are regulated by chemokine (C‐X‐C motif) receptor ( CXCR ) 4 and atypical chemokine receptor 3 ( ACKR 3). While we showed that CXCR 4 controls α 1 ‐ ARs through formation of heteromeric receptor complexes in human vascular smooth muscle cells ( hVSMCs ), the molecular basis underlying cross‐talk between ACKR 3 and α 1 ‐ ARs is unknown. Methods and Results We show that ACKR 3 agonists inhibit inositol trisphosphate production in hVSMCs on stimulation with phenylephrine. In proximity ligation assays and co‐immunoprecipitation experiments, we observed that recombinant and endogenous ACKR 3 form heteromeric complexes with α 1A/B/D ‐ AR . While small interfering RNA knockdown of ACKR 3 in hVSMCs reduced α 1B/D ‐ AR : ACKR 3, CXCR 4: ACKR 3, and α 1B/D ‐ AR : CXCR 4 complexes, small interfering RNA knockdown of CXCR 4 reduced α 1B/D ‐ AR : ACKR 3 heteromers. Phenylephrine‐induced inositol trisphosphate production from hVSMCs was abolished after ACKR 3 and CXCR 4 small interfering RNA knockdown. Peptide analogs of transmembrane domains 2/4/7 of ACKR 3 showed differential effects on heteromerization between ACKR 3, α 1A/B/D ‐ AR, and CXCR 4. While the transmembrane domain 2 peptide interfered with α 1B/D ‐ AR : ACKR 3 and CXCR 4: ACKR 3 heteromerization, it increased heteromerization between CXCR 4 and α 1A/B ‐ AR . The transmembrane domain 2 peptide inhibited ACKR 3 but did not affect α 1b ‐ AR in β‐arrestin recruitment assays. Furthermore, the transmembrane domain 2 peptide inhibited phenylephrine‐induced inositol trisphosphate production in hVSMCs and attenuated phenylephrine‐induced constriction of mesenteric arteries. Conclusions α 1 ‐ ARs form hetero‐oligomeric complexes with the ACKR 3: CXCR 4 heteromer, which is required for α 1B/D ‐ AR function, and activation of ACKR 3 negatively regulates α 1 ‐ AR s. G protein–coupled receptor hetero‐oligomerization is a dynamic process, which depends on the relative abundance of available receptor partners. Endogenous α 1 ‐ AR s function within a network of hetero‐oligomeric receptor complexes.
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- 2017
23. Expression of α1 adrenergic receptor subtypes by afferent fibers that innervate rat massetermuscle
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Hayes Wong, Brian E. Cairns, and J. Liu
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Masseter muscle ,medicine.medical_specialty ,Anesthesiology and Pain Medicine ,Endocrinology ,business.industry ,Internal medicine ,Afferent ,Medicine ,Neurology (clinical) ,Anatomy ,business ,α1 adrenergic receptor - Abstract
Aims In temporomandibular disorders sufferers, muscle pain is more severe in individuals who have undergone a traumatic stress. Why stress exacerbates masticatory muscle pain in these individuals is not known. One possibility is that under conditions of stress there is an interaction between the sympathetic and sensory nervous systems. This study investigated whether trigeminal ganglion neurons that innervate the masseter muscle express α1 adrenergic receptor subtypes to identify whether a direct interaction between the sympathetic and sensory nervous systems is feasible. Methods Masseter muscle ganglion neurons were identified by injection of the fluorescent dye fast blue into the masseter muscle of 4 Sprague Dawley rats (2 male, 2 female). Trigeminal ganglion sections were stained for α1a, α1b or α1d adrenergic receptors, as well as the transient receptor potential vanilloid 1 (TrpV1) receptor. Sections were examined with a Leica confocal microscope. The percent of masseter ganglion neurons expressing each receptor was calculated. Results Masseter muscle ganglion neurons expressed α1a(29 ± 9%), α1b (34 ± 4%) and α1d (19 ± 13%) adrenergic receptors. Expression of all three α1 receptor subtypes was higher in female rats than in male rats. Expression of α1b receptors was more commonly found on larger diameter masseter ganglion neurons. Overall 11±3% of masseter ganglion neurons expressed the TrpV1 receptor, which suggests they served a nociceptive function. The TrpV1 receptor was co-expressed by about ~10% of α1a and α1b receptor positive masseter ganglion neurons. Conclusions Afferent fibers that innervate the masseter muscle express all three α1 adrenergic receptor subtypes. Agonists at the α1 receptor have been previously shown to depolarize trigeminal ganglion neurons, which suggests that activation of these receptors on masseter muscle afferents would be excitatory. The expression of α1 receptors by putative nociceptors that innervate the masseter may permit a direct interaction between the sensory and sympathetic system that contributes to pain in this muscle.
- Published
- 2017
24. Effect of prazosin on diabetic nephropathy patients with positive α1-adrenergic receptor autoantibodies and refractory hypertension
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Lin-Shuang Zhao and Chun-Yan Xu
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Cancer Research ,medicine.medical_specialty ,prazosin ,business.industry ,autoantibodies ,Autoantibody ,Cancer ,diabetic nephropathy with refractory hypertension ,General Medicine ,Articles ,medicine.disease ,α1 adrenergic receptor ,Molecular medicine ,Gastroenterology ,Pathogenesis ,Diabetic nephropathy ,Endocrinology ,Immunology and Microbiology (miscellaneous) ,Refractory ,Internal medicine ,medicine ,Prazosin ,business ,Receptor ,medicine.drug - Abstract
To investigate the effect of prazosin on patients with diabetic nephropathy (DN), α1-adrenergic receptor (α1-R) autoantibodies and refractory hypertension, a total of 126 patients with DN and hypertension were recruited. The patients were divided into a refractory hypertension group, (n=76) and a non-refractory hypertension group (n=50). The epitope of the second extracellular loop of the α1-R (192–218) was synthesized and an enzyme-linked immunosorbent assay (ELISA) was performed to detect serum autoantibodies. In the group with DN-associated refractory hypertension, the positive rate of autoantibodies against the α1-R was 80.3% (n=61). The 61 patients who were positive for α1-R autoantibodies were randomly divided into a treatment group (n=31) and a control group (n=30). The patients were given drugs at the same dosage and administration, with the exception of prazosin, which was provided only to the patients in the treatment group [1 mg, three times a day (tid)] for a duration of six weeks. Subsequently, prazosin was added (1 mg, tid) to the therapeutic schedule of the patients in the control group and the α1-R autoantibody-negative group for another six weeks. The analysis was carried out on an intention-to-treat basis. The prazosin treatment resulted in significant improvements in hypertension in the treatment group (P
- Published
- 2014
25. Re: The Efficacy of Mirabegron Additional Therapy for Lower Urinary Tract Symptoms after Treatment with Α1-Adrenergic Receptor Blocker Monotherapy: Prospective Analysis of Elderly Men
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Miki Yuzuriha, Hideki Sakai, Yasuyoshi Miyata, Akihiro Asai, Katsura Kakoki, Tomohiro Matsuo, and Kojiro Ohba
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Male ,Additional Therapy ,030232 urology & nephrology ,Prostatic Hyperplasia ,Pharmacology ,urologic and male genital diseases ,01 natural sciences ,Prospective analysis ,0302 clinical medicine ,Prospective Studies ,Prospective cohort study ,Aged, 80 and over ,Elderly male ,General Medicine ,Receptors, Adrenergic ,Treatment Outcome ,Overactive bladder ,030220 oncology & carcinogenesis ,International Prostate Symptom Score ,Drug Therapy, Combination ,After treatment ,medicine.drug ,Research Article ,Agonist ,medicine.medical_specialty ,medicine.drug_class ,Urology ,Adrenergic beta-3 Receptor Agonists ,α1 adrenergic receptor ,03 medical and health sciences ,Text mining ,Lower Urinary Tract Symptoms ,Lower urinary tract symptoms ,Internal medicine ,medicine ,Humans ,Aged ,Mirabegron ,010405 organic chemistry ,business.industry ,Urinary Bladder, Overactive ,α1-adrenergic blockers ,medicine.disease ,0104 chemical sciences ,Thiazoles ,Reproductive Medicine ,Adrenergic alpha-1 Receptor Antagonists ,Acetanilides ,business - Abstract
Mirabegron is a β3-adrenoreceptor agonist developed for treatment of overactive bladder (OAB). α1-Adrenergic receptor blockers are effective for lower urinary tract symptoms (LUTS) in male patients. However, the efficacy of mirabegron additional treatment in elderly male patients with persistent male LUTS, especially in OAB after monotherapy with α1-adrenergic blockers, is not fully understood. This study was conducted in male LUTS patients who were ≥ 65 years of age and had persistent OAB symptoms, regardless of whether they took an α1-adrenergic receptor blocker orally. Before and 12 weeks after mirabegron additional therapy (50 mg once daily), we evaluated the efficacy of this treatment using the Overactive Bladder Symptom Score (OABSS) and International Prostate Symptom Score (IPSS), and changes in the maximum flow rate (Qmax) and post-void residual urine volume (PVR). We evaluated patients overall and divided into two groups by age: young-old (from 65 to 74 years old) and old-old (from 75 to 84 years old). Fifty men were enrolled in this study. Mirabegron additional therapy improved the total OABSS, total IPSS, and IPSS-quality of life (QOL) score. The voided volume (VV) and Qmax improved after treatment in patients overall. However, there was no significant change in PVR. The total OABSS, total IPSS, and IPSS-QOL score significantly improved in both of the young-old and old-old groups. However, a significant increasing of VV was detected in the young-old group. There were no significant differences in the Qmax or PVR in either group. Mirabegron additional therapy was effective for male patients whose persistent LUTS and particularly OAB was not controlled with α1-adrenergic receptor blocker monotherapy, and mirabegron did not have negative effects on voiding function. Additionally, mirabegron additional therapy was considered effective regardless of patient age. Trial registration number (TRN) trial registration number (TRN) and date of registration: ISRCTN16759097 in July 8, 2016.
- Published
- 2016
26. α1-Adrenergic receptor subtypes in the central nervous system: insights from genetically engineered mouse models
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Irena Nalepa, Grzegorz Kreiner, Adam Bielawski, Katarzyna Rafa-Zabłocka, and Adam Roman
- Subjects
Central Nervous System ,Pharmacology ,Central nervous system ,General Medicine ,Biology ,α1 adrenergic receptor ,Phenotype ,Animals, Genetically Modified ,Mice ,Adrenergic Agents ,medicine.anatomical_structure ,Receptors, Adrenergic, alpha-1 ,Genetically Engineered Mouse ,Genetic model ,medicine ,Animals ,Humans ,Receptor ,Neuroscience ,Function (biology) ,Intracellular - Abstract
α1-Adrenergic receptors (α1-ARs) are important players in peripheral and central nervous system (CNS) regulation and function and in mediating various behavioral responses. The α1-AR family consists of three subtypes, α1A, α1B and α1D, which differ in their subcellular distribution, efficacy in evoking intracellular signals and transcriptional profiles. All three α1-AR subtypes are present at relatively high densities throughout the CNS, but the contributions of the individual subtypes to various central functions are currently unclear. Because of the lack of specific ligands, functionally characterizing the α1-ARs and discriminating between the three subtypes are difficult. To date, studies using genetically engineered mice have provided some information on subtype-related functions of the CNS α1-ARs. In this mini-review, we discuss several CNS processes where the α1-ARs role has been delineated with pharmacological tools and by studies using mutated mice strains that infer specific α1-AR subtype functions through evaluation of behavioral phenotypes.
- Published
- 2013
27. KCNQ1 is internalized by activation of α1 adrenergic receptors.
- Author
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Kurakami, Kazuya, Norota, Ikuo, Nasu, Fumiaki, Ohshima, Shingo, Nagasawa, Yoshinobu, Konno, Yoshihiro, Obara, Yutaro, and Ishii, Kuniaki
- Subjects
- *
ADRENERGIC receptors , *POTASSIUM channels , *CONFOCAL fluorescence microscopy , *CELL membranes , *KINASES - Abstract
KCNQ1 (Kv7.1 or KvLQT1) plays important physiological roles in various tissues forming potassium channels with KCNE subunits. Among the channels formed by KCNQ1 and KCNE subunits, the best studied is the slow delayed rectifier potassium channel in the heart, the I Ks (KCNQ1/KCNE1) channel, which is critical for repolarization of cardiac action potential. The KCNQ1 channel is internalized by Nedd4/Nedd4-like ligase-dependent ubiquitination. It is also reported that phosphorylation of KCNE1 by PKC results in internalization of the KCNQ1/KCNE1 channel. Because we have observed down-regulation of KCNQ1/KCNE1 currents by activation of the α 1 -adrenergic receptor (α 1 AR) that activates PKC, this study investigated whether α 1 AR causes internalization of the KCNQ1 protein. We fused HaloTag to the extracellular region of KCNQ1 (Halo-KCNQ1) and co-expressed it with α 1 ARs in HEK293 cells. The KCNQ1 protein on the cell surface was selectively labeled with membrane-impermeable HaloTag ligands, and changes in its localization were monitored by confocal fluorescence microscopy. Activation of α 1A AR and α 1B AR caused marked internalization of KCNQ1, which was not KCNE1-dependent. Internalization of KCNQ1 by α 1 AR activation was inhibited by disruption of the PY motif or the YXXΦ motif in the C-terminus. Double staining for the receptor and the channel revealed that KCNQ1 internalization was independent of α 1 AR internalization. Our results suggest that α 1 AR-mediated direct internalization of KCNQ1 is AP2/clathrin-dependent and may be triggered by ubiquitination of KCNQ1 via the AMP dependent kinase (AMPK)/Nedd4-2 pathway. When phenylephrine was applied to rat neonatal cardiomyocytes transfected with KCNQ1 and α 1 AR, the KCNQ1 protein was internalized. The internalization of KCNQ1 by α 1 AR would affect pathophysiology in a variety of tissues expressing KCNQ1, which merits further in vivo study. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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28. Sustained in vivo blockade of α1-adrenergic receptors prevented some of stress-triggered effects on steroidogenic machinery in Leydig cells
- Author
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Aleksandar I. Mihajlović, Maja M. Bjelic, Aleksandar Z. Baburski, Marija M. Janjic, Silvana A. Andric, Dragana M. Drljaca, Natasa J. Stojkov, Tatjana S. Kostic, and Srdjan J. Sokanovic
- Subjects
medicine.medical_specialty ,Physiology ,Endocrinology, Diabetes and Metabolism ,Biology ,α1 adrenergic receptor ,Blockade ,Endocrinology ,In vivo ,Physiology (medical) ,Internal medicine ,medicine ,Doxazosin ,Receptor ,Testosterone ,medicine.drug - Abstract
This study was designed to systematically analyze and evaluate the effects of in vivo blockade of α1-adrenergic receptors (α1-ADRs) on the stress-induced disturbance of steroidogenic machinery in Leydig cells. Parameters followed 1) steroidogenic enzymes/proteins, transcription factors, and cAMP/testosterone production; 2) the main hallmarks of stress (epinephrine, glucocorticoids); and 3) transcription profiles of ADRs and oxidases with high affinity to inactivate glucocorticoids. Results showed that sustained blockade of α1-ADRs prevented stress-induced 1) decrease of the transcripts/proteins for main steroidogenic CYPs (CYP11A1, CYP17A1); 2) decrease of Scarb1 and Hsd3b1 transcripts; 3) decrease of transcript for Nur77, one of the main activator of the steroidogenic expression; and 4) increase of Dax1 and Arr19, the main steroidogenic repressors in Leydig cells. In the same cells, the expression of steroidogenic stimulatory factor Creb1, StAR, and androgen receptor increased. In this signaling scenario, stress-induced stimulation of Adra1a/Adra1b/Adrbk1 and Hsd11b2 (the unidirectional oxidase with high affinity to inactivate glucocorticoids) was not changed. Blockade additionally stimulated stress-increased transcription of the most abundantly expressed ADRs Adra1d/Adrb1/Adrb2 in Leydig cells. In the same cells, stress-decreased testosterone production, the main marker of Leydig cells functionality, was completely prevented, while reduction of cAMP, the main regulator of androgenesis, was partially prevented. Accordingly, the presented data provide a new molecular/transcriptional base for “fight/adaptation” of steroidogenic cells and new molecular insights into the role of α1-ADRs in stress-impaired Leydig cell steroidogenesis. The results are important in term of wide use of α1-ADR selective antagonists, alone/in combination, to treat high blood pressure, nightmares associated with posttraumatic stress disorder, and disrupted sexual health.
- Published
- 2013
29. Asymmetric Cyanoethoxy Carbonylation Reaction of Aldehydes Catalyzed by a TiIVMacrocyclic Complex: An Efficient Synthetic Protocol for β-Blocker and α1-Adrenergic Receptor Agonists
- Author
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Hari C. Bajaj, Sayed H. R. Abdi, Rukhsana I. Kureshy, Noor-ul H. Khan, Arghya Sadhukhan, and Manoj K. Choudhary
- Subjects
Inorganic Chemistry ,Chemistry ,Stereochemistry ,Organic Chemistry ,Physical and Theoretical Chemistry ,α1 adrenergic receptor ,Carbonylation ,Catalysis - Published
- 2013
30. The opposite roles of glucocorticoid and α1-adrenergic receptors in stress triggered apoptosis of rat Leydig cells
- Author
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Aleksandar Z. Baburski, Stanko S. Stojilkovic, Aleksandar I. Mihajlović, Tatjana S. Kostic, Marija M. Janjic, Natasa J. Stojkov, Zvezdana Kojic, Silvana A. Andric, Maja M. Bjelic, and Srdjan J. Sokanovic
- Subjects
Male ,endocrine system ,medicine.medical_specialty ,Physiology ,Endocrinology, Diabetes and Metabolism ,Adrenergic ,Apoptosis ,Biology ,α1 adrenergic receptor ,Immobilization ,03 medical and health sciences ,chemistry.chemical_compound ,Receptors, Glucocorticoid ,0302 clinical medicine ,Corticosterone ,Receptors, Adrenergic, alpha-1 ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Rats, Wistar ,Receptor ,Glucocorticoids ,Cells, Cultured ,030304 developmental biology ,0303 health sciences ,Leydig Cells ,Articles ,Mitochondria ,Rats ,Endocrinology ,chemistry ,Glucocorticoid metabolism ,Drug Antagonism ,Stress, Psychological ,030217 neurology & neurosurgery ,Glucocorticoid ,Signal Transduction ,medicine.drug - Abstract
The stress-induced initiation of proapoptotic signaling in Leydig cells is relatively well defined, but the duration of this signaling and the mechanism(s) involved in opposing the stress responses have not been addressed. In this study, immobilization stress (IMO) was applied for 2 h daily, and animals were euthanized immediately after the first (IMO1), second (IMO2), and 10th (IMO10) sessions. In IMO1 and IMO2 rats, serum corticosterone and adrenaline were elevated, whereas serum androgens and mRNA transcription of insulin-like factor-3 in Leydig cells were inhibited. Reduced oxygen consumption and the mitochondrial membrane potential coupled with a leak of cytochrome c from mitochondria and increased caspase-9 expression, caspase-3 activity, and number of apoptotic Leydig cells was also observed. Corticosterone and adrenaline were also elevated in IMO10 rats but were accompanied with a partial recovery of androgen secretion and normalization of insulin-like factor-3 transcription coupled with increased cytochrome c expression, abolition of proapoptotic signaling, and normalization of the apoptotic events. Blockade of intratesticular glucocorticoid receptors diminished proapoptotic effects without affecting antiapoptotic effects, whereas blockade of intratesticular α1-adrenergic receptors diminished the antiapoptotic effects without affecting proapoptotic effects. These results confirmed a critical role of glucocorticoids in mitochondria-dependent apoptosis and showed for the first time the relevance of stress-induced upregulation of α1-adrenergic receptor expression in cell apoptotic resistance to repetitive IMOs. The opposite role of two hormones in control of the apoptotic rate in Leydig cells also provides a rationale for a partial recovery of androgen production in chronically stressed animals.
- Published
- 2013
31. Modulation of Alpha 1 Adrenergic Receptors on Urinary Bladder in Rat Spinal Cord Injury Model
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Gilho Lee, Heeyoon Park, Jeong Gu Lee, and Hong Suk Park
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Pathology ,medicine.medical_specialty ,Urinary bladder ,Adrenergic receptor ,business.industry ,Urology ,Alpha (ethology) ,Alpha adrenergic receptors ,medicine.disease ,lcsh:Diseases of the genitourinary system. Urology ,lcsh:RC870-923 ,α1 adrenergic receptor ,medicine.anatomical_structure ,Basic Research ,Neurology ,medicine ,Spinal cord injuries ,Original Article ,Neurology (clinical) ,business ,Spinal cord injury - Abstract
Purpose Whereas many studies have focused on the vesical changes of the α1 adrenergic receptor (AR) subtypes in partial outlet obstruction, few studies have addressed the modulation of the α1 AR subtypes after spinal cord injury (SCI). Therefore, we studied the modulation of the α1 ARs in urinary bladder in a rat SCI model. Methods Four weeks after a SCI, the whole vesical bodies from eight female Sprague-Dawley rats and from eight controls were harvested. The total RNA was extracted from the samples and was used to prepare cDNA. We developed standard plasmid constructs of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and three α1 ARs (α1a, α1b, and α1d) to convert the cycle threshold (Ct) values from real-time polymerase chain reaction (RT-PCR) into subtype mRNA concentrations. The detected Ct values of 16 samples from RT-PCR were interpolated into the standard plasmid curves. Results All serially diluted standard samples showed very good linearity. The mRNA expression of GAPDH was higher in the SCI group, whereas the mRNA expression of all α1 ARs was lower in the SCI group than in the control animals. The α1a, α1b, and α1d mRNA expression in the controls was 81.7%, 3.3%, and 15.1%, respectively, whereas the α1a, α1b, and α1d mRNA expression in the SCI group was 33.5%, 5.2%, and 60.9%, respectively. Conclusions SCI moderates the α1 AR mRNA subtypes in the urinary bladder. The relatively increased α1d or decreased α1a AR mRNA expression may be a therapeutic candidate for controlling the symptoms of neurogenic bladder after SCI.
- Published
- 2012
32. Relaxant effects of Aike Mixture (艾可合剂) on isolated bladder and prostatic urethral smooth muscle of rabbits
- Author
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Zhen-wei Li, Ya-lei Shi, Min-jian Zhang, Xiang Lin, and Wan-jun Cheng
- Subjects
Male ,medicine.medical_specialty ,Urinary Bladder ,Adrenergic ,In Vitro Techniques ,Hydroxylamines ,α1 adrenergic receptor ,Calcium Chloride ,Urethra ,Smooth muscle ,Receptors, Adrenergic, alpha-1 ,Internal medicine ,Animals ,Medicine ,Pharmacology (medical) ,Receptor ,business.industry ,Prostate ,Muscle, Smooth ,General Medicine ,Receptors, Muscarinic ,Endocrinology ,Neuromuscular Agents ,Complementary and alternative medicine ,Medicine public health ,Carbachol ,Ca2 channels ,Rabbits ,business ,Drugs, Chinese Herbal ,Muscle Contraction - Abstract
To observe the relaxant effect of Aike Mixture (AKM) on isolated bladder and prostatic urethral smooth muscle of rabbits.The isolated bladder and prostatic urethral smooth muscle from male rabbits were placed in a Magnus bath and smooth muscle contraction was measured using a biological signal acquisition and analysis system. The effects of AKM in combination with methoxyamine, carbachol and CaCl2 on the contractile tension of muscle strips were determined by cumulative dosing.AKM dose-dependently reduced contractile tension of bladder trigone smooth muscle (r=0.831, P0.05), reduced contractile wave amplitude (r=0.837, P0.05) and decreased contractile frequency (r=-0.917, P0.01). AKM significantly inhibited the increases in smooth muscle contraction induced by methoxyamine, carbachol and CaCl2.AKM dose-dependently inhibited the contraction of rabbit isolated bladder and prostatic urethral smooth muscle by antagonizing α1-adrenergic receptors and M-cholinergic receptors.
- Published
- 2012
33. Alkaloids and Flavonoids as α1-Adrenergic Receptor Antagonists
- Author
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Lupei Du, Minyong Li, and Wenhua Li
- Subjects
Pharmacology ,Drug ,Chemistry ,medicine.drug_class ,media_common.quotation_subject ,Organic Chemistry ,Receptor antagonist ,Biochemistry ,α1 adrenergic receptor ,Drug Discovery ,medicine ,Molecular Medicine ,Structure–activity relationship ,Receptor ,media_common - Abstract
Since the subtypes of α(1)-adrenergic receptor have been thoroughly determined, to date medicinal chemists raise their deliberation on how to conceive selective α(1)-adrenergic receptor antagonist with the minimal side effects. It needs to be well recognized that natural products can exist as a significant source of drug leads, thus portraying a consequential capacity in drug design and development. The current review article would like to present a comprehensive survey on natural products, mainly including alkaloids and flavonoids, which exhibit α(1)-adrenergic receptor antagonistic activities.
- Published
- 2011
34. Role of supraspinal and spinal α1-adrenergic receptor subtypes in micturition reflex in conscious rats
- Author
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Akihiko Yonezawa, Masahito Kawatani, Masaru Yoshizumi, and Kazumasa Matsumoto-Miyai
- Subjects
Tamsulosin ,medicine.medical_specialty ,Indoles ,Consciousness ,Physiology ,Urinary system ,media_common.quotation_subject ,Central nervous system ,Urination ,α1 adrenergic receptor ,Receptors, Adrenergic, alpha-1 ,Internal medicine ,Reflex ,medicine ,Animals ,Rats, Wistar ,Receptor ,Adrenergic alpha-Antagonists ,Injections, Spinal ,Injections, Intraventricular ,media_common ,Sulfonamides ,Dose-Response Relationship, Drug ,business.industry ,Antagonist ,Brain ,Spinal cord ,Rats ,medicine.anatomical_structure ,Endocrinology ,Spinal Cord ,Models, Animal ,Adrenergic alpha-1 Receptor Antagonists ,Female ,business - Abstract
α1-Adrenergic receptor subtypes are widely distributed in the central nervous system and are involved in autonomic functions such as micturition. We investigated the presence and the role of supraspinal and/or spinal α1-adrenergic receptors in modulating the micturition reflex in conscious female Wistar rats. The expression of α1-adrenergic receptor subtypes in rat brain and lumbosacral spinal cord was studied using RT-PCR. Continuous-infusion cystometrograms were obtained in conscious rats, and α1-adrenergic receptor antagonists were administered via intracerebroventricular or intrathecal routes. The mRNA expression of α1A-, α1B-, and α1D-adrenergic receptors was detected in rat brain (midbrain and pons) and lumbosacral spinal cord (dorsal and ventral parts of spinal cord). In addition, intracerebroventricular injection of the α1-adrenergic receptor antagonist tamsulosin (1–10 μg), the selective α1A-adrenergic receptor antagonist silodosin (1–10 μg), and the selective α1D-adrenergic receptor antagonist BMY 7378 (1–10 μg) significantly prolonged the intercontraction interval (ICI) but did not alter maximum voiding pressure (MVP). Although intrathecal injection of BMY 7378 (0.0001–10 μg) did not affect ICI, tamsulosin and silodosin prolonged ICI in a dose-dependent manner. MVP was significantly reduced by intrathecal injection of tamsulosin (10 μg) but not by silodosin or BMY 7378 (0.0001–10 μg). Supraspinal α1A- and α1D-adrenergic receptors are apparently important for the regulation of reflex-bladder activity in conscious rats. Noradrenergic projection from the brain stem to the lumbosacral spinal cord may promote the afferent limb rather than the efferent limb of the micturition reflex pathway via α1A-adrenergic receptors.
- Published
- 2010
35. Up-Down Determination of the 90% Effective Dose of Phenylephrine for the Treatment of Spinal Anesthesia-Induced Hypotension in Parturients Undergoing Cesarean Delivery
- Author
-
Dolores M. McKeen, Malachy O. Columb, Ashraf S. Habib, and Ronald B. George
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Blood Pressure ,Anesthesia, Spinal ,α1 adrenergic receptor ,Cohort Studies ,Phenylephrine ,Young Adult ,Pregnancy ,Anesthesia, Obstetrical ,Humans ,Vasoconstrictor Agents ,Medicine ,Antihypotensive agent ,Cesarean delivery ,Induced Hypotension ,Cesarean Section ,business.industry ,Spinal anesthesia ,medicine.disease ,Effective dose (pharmacology) ,Surgery ,Logistic Models ,Anesthesiology and Pain Medicine ,Anesthesia ,Female ,Hypotension ,business ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Hypotension frequently complicates spinal anesthesia for cesarean delivery, and vasopressors are the mainstay for treatment. The most effective dose of phenylephrine for the treatment of spinal anesthesia-induced hypotension has not been estimated.Healthy nonlaboring women undergoing a cesarean delivery were recruited. All women received spinal anesthesia using hyperbaric bupivacaine 12 mg with fentanyl and morphine. Each subject received an i.v. crystalloid fluid bolus before and at the time of initiation of spinal anesthesia (preload and coload). An up-down sequential allocation method using the biased-coin design was used to estimate the 90% effective dose (ED(90)) of phenylephrine. The assigned phenylephrine dose was based on the response of the preceding subject. If the systolic blood pressure (SBP) decreased20% of baseline (i.e., SBP 20%) or to an SBP90 mm Hg, the assigned dose of phenylephrine was administered. If the SBP returned to within 20% of baseline oror = 90 mm Hg within 1 min, this was considered a success, otherwise it was a failure. The initial dose of phenylephrine was 100 microg. The ED(90) with 95% confidence intervals (CIs) was calculated using the maximum likelihood estimation and Firth logistic regression.Sixty-nine subjects were screened to participate, of whom 66 subjects consented. Forty-five of the enrolled subjects experienced spinal anesthesia-induced hypotension and received a blinded dose of phenylephrine. Those subjects who developed hypotension received doses of phenylephrine between 80 and 180 microg. No subjects experienced hypertension. Determined with the maximum likelihood estimation method, the ED(90) of phenylephrine was 147 microg (95% CI, 98-222 microg). With Firth regression, the probability of a successful response at 150 microg is 90.5% (95% CI, 66.0%-99.0%).In this study, we estimated that the ED(90) of phenylephrine required to treat spinal anesthesia-induced hypotension in cesarean delivery is approximately 150 microg.
- Published
- 2010
36. The Effects of Tolterodine Extended Release and Alfuzosin for the Treatment of Double-J Stent–Related Symptoms
- Author
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Seung Chol Park, Jea Whan Lee, Sung Won Jung, and Joung Sik Rim
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Tolterodine Tartrate ,Urology ,Phenylpropanolamine ,Muscarinic Antagonists ,α1 adrenergic receptor ,Cresols ,Young Adult ,Postoperative Complications ,Lower urinary tract symptoms ,Surveys and Questionnaires ,Humans ,Medicine ,Benzhydryl Compounds ,Alfuzosin ,Adrenergic alpha-Antagonists ,Aged ,Demography ,Aged, 80 and over ,Quinazoline derivatives ,Alfuzosina ,business.industry ,Middle Aged ,medicine.disease ,Delayed-Action Preparations ,Double j stent ,Anesthesia ,Quinazolines ,Female ,Stents ,Tolterodine ,Extended release ,business ,medicine.drug - Abstract
To evaluate the effects of tolterodine extended release (ER) and alfuzosin for the treatment of Double-J stent-related lower urinary tract symptoms.Fifty-two patients (33 men and 19 women; mean age 52.0 years) who underwent insertion of a Double-J stent after urological surgery were prospectively randomized into three groups. Group 1 included 20 patients who received 10 mg of alfuzosin, once daily for 6 weeks; group 2 included 20 patients who received 4 mg of tolterodine ER, once daily for 6 weeks; group 3 included 12 patients who received a placebo for the same protocol. All patients completed a validated Ureteral Stent Symptom Questionnaire at 6 weeks after the stent placement.The mean urinary symptom index was 22.1 in group 1, 22.1 in group 2, and 28.1 in the placebo group (p = 0.032). The mean pain scores were 8.2, 11.7, and 16.2, respectively (p = 0.020). There were no significant differences in urinary symptoms and pain between the alfuzosin and tolterodine ER groups. In addition, there was no significant difference in the general health, work performance, and sexual performance scores among the groups.Tolterodine ER and alfuzosin improve stent-related urinary symptoms and body pain.
- Published
- 2009
37. Effect of Halothane on Calf Cortex α1-Adrenoceptors
- Author
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A. R. Hede, M. Lindahl, and J. E. S. Wikberg
- Subjects
Cerebral Cortex ,Pharmacology ,medicine.medical_specialty ,Chemistry ,Central nervous system ,Prazosin ,In Vitro Techniques ,Receptors, Adrenergic, alpha ,Tritium ,Toxicology ,α1 adrenoceptor ,α1 adrenergic receptor ,medicine.anatomical_structure ,Endocrinology ,Mechanism of action ,Internal medicine ,Cortex (anatomy) ,medicine ,Animals ,Cattle ,medicine.symptom ,Halothane ,medicine.drug - Published
- 2009
38. Gene expressions and mechanical functions of α1-adrenoceptor subtypes in mouse ureter
- Author
-
Yasue Kubota, Yoshitaka Tomiyama, Yoshinobu Yamazaki, Hiroshi Kusama, Kenjiro Kohri, Yasunori Itoh, Yuji Hoyano, and Shinya Kobayashi
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Indoles ,Epinephrine ,Urology ,Urinary stone ,Gene Expression ,Biology ,α1 adrenergic receptor ,Piperazines ,Mice ,Norepinephrine ,Ureter ,Receptors, Adrenergic, alpha-1 ,Gene expression ,medicine ,Animals ,RNA, Messenger ,Gene ,Mice, Inbred ICR ,Messenger RNA ,Prazosin ,Mouse Ureter ,α1 adrenoceptor ,Cell biology ,medicine.anatomical_structure ,Adrenergic alpha-1 Receptor Antagonists ,Muscle Contraction - Abstract
This study was performed to characterize the α1-adrenoceptor subtypes in mouse ureters as regards gene expressions and contractile functions.The mRNAs for these subtypes were quantified by the real-time quantitative reverse transcription polymerase chain reaction. In a functional study, α1-adrenoceptor antagonists were evaluated against the noradrenaline-induced contraction in mouse isolated ureteral preparations.In mouse ureter, the relative mRNA expression levels for α1a-, α1b- and α1d-adrenoceptors were 74.5, 14.3 and 11.2%, respectively. Adrenaline and noradrenaline each produced a concentration-dependent phasic contraction (pD 2 values, 5.73±0.05 and 5.69±0.06, respectively). Prazosin (non-selective α1-adrenoceptor antagonist), silodosin (selective α1A-adrenoceptor antagonist), and BMY-7378 (selective α1D-adrenoceptor antagonist) all shifted the concentration–response curve for noradrenaline to the right, the rank order of potencies (apparent pA 2 values) being silodosin (9.32±0.11)prazosin (8.55±0.10)BMY-7378 (6.06±0.15). The α1A-adrenoceptor antagonist silodosin was thus much more effective than the α1D-adrenoceptor antagonist BYM-7378.Our results demonstrate that in mouse ureters: the mRNA for the α1A-adrenoceptor was more prevalent than those for the α1B- and α1D-adrenoceptors, and that among these subtypes, the α1A-adrenoceptor plays the major role in noradrenaline-induced contraction.
- Published
- 2009
39. α1a/1d-selective adrenergic receptor antagonists for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms
- Author
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Steven A. Middleton, Allen B. Reitz, Virginia L. Pulito, George Chiu, Ellen W. Baxter, Peter J. Connolly, Jingchun Liu, and Shengjian Li
- Subjects
Pharmacology ,medicine.medical_specialty ,business.industry ,Urology ,Antagonist ,General Medicine ,Subtype selective ,Hyperplasia ,Highly selective ,medicine.disease ,α1 adrenergic receptor ,Pharmacokinetics ,Lower urinary tract symptoms ,Adrenergic receptor antagonists ,Drug Discovery ,Medicine ,business - Abstract
Background: Although α1 adrenergic receptor blockers can be very effective for the treatment of benign prostatic hyperplasia/lower urinary tract symptoms (BPH/LUTS), their usage is limited by cardiovascular-related side effects that are caused by the subtype nonselective nature of many current drugs. To overcome this problem, it was hypothesized that an α1a/1d subtype selective antagonist would be efficacious yet produce less side effects, and hence would bring greater benefit for the therapy of BPH/LUTS. Unfortunately, such highly selective α1a/1d antagonists were not available, making the validation of the new hypothesis impossible. Objective/method: This review disclosed several series of α1a/1d subtype selective antagonists that have been discovered and developed by Johnson & Johnson recently. These compounds show equal and potent affinity for both α1a and α1d subtypes with good selectivity versus the α1b subtype. Some analogues also possess favorable pharmacokinetic properties. Conclusion: Although d...
- Published
- 2008
40. Recent advances in selective α1-adrenoreceptor antagonists as antihypertensive agents
- Author
-
Anamik Shah, Bishram S. Chauhan, Manisha S. Phoujdar, Jitender Bariwal, Kishor S. Jain, Rajkumari S. Sahne, M. K. Kathiravan, and Mange Ram Yadav
- Subjects
Drug ,media_common.quotation_subject ,Clinical Biochemistry ,Pharmaceutical Science ,Alpha (ethology) ,Imidazoline derivatives ,Pharmacology ,Biochemistry ,α1 adrenergic receptor ,Structure-Activity Relationship ,Health problems ,Risk Factors ,Receptors, Adrenergic, alpha-1 ,Drug Discovery ,Animals ,Humans ,Molecular Biology ,Adrenergic alpha-Antagonists ,Antihypertensive Agents ,media_common ,Quinazoline derivatives ,Molecular Structure ,Chemistry ,Organic Chemistry ,Stereoisomerism ,Hypertension ,Adrenergic alpha-1 Receptor Antagonists ,Molecular Medicine ,Dihydropyridine derivatives - Abstract
Hypertension is one of the most serious health problems of the modern world with a continuous rise in the number of patients. Selective alpha(1)-adrenoreceptor antagonists though have many advantages and uses in the management of arterial hypertension, their lack of specificity at the level of alpha(1)-adr subtypes leads to multiple side effects. Existence of multiple alpha(1)-adr subtypes holds great promise for the discovery and development of more specific and selective drug molecules, targeting only one alpha(1)-adr subtype at a time and thus relative freedom from side effects. Herein, the research done on the discovery and evaluation of a variety of chemically diverse structures as selective antagonists of alpha(1)-adr and alpha(1)-adr subtypes in recent years has been reviewed.
- Published
- 2008
41. Computational Modeling of Selective Pharmacophores at the α1‐Adrenergic Receptors
- Author
-
Pier G. De Benedetti and Francesca Fanelli
- Subjects
Quantitative structure–activity relationship ,Stereochemistry ,Chemistry ,Pharmacophore ,α1 adrenergic receptor ,G protein-coupled receptor - Published
- 2008
42. Rachianesthésie pour césarienne: remplissage, vasopresseurs et hypotension
- Author
-
F. Banu, M. Moufouki, A. De la Dorie, Frédéric J. Mercier, A. Hanaf, D. Édouard, M.-P. Bonnet, and S. Roger-Christoph
- Subjects
Gynecology ,medicine.medical_specialty ,α adrenergic receptors ,Vena cava ,Philosophy ,Arterial hypotension ,Fluid loading ,Crystalloid solutions ,Spinal anesthesia ,General Medicine ,α1 adrenergic receptor ,Anesthesiology and Pain Medicine ,medicine ,β adrenergic receptor - Abstract
Resume Objectif Analyser les differentes strategies preventives et therapeutiques de prise en charge de l'hypotension arterielle au cours de la rachianesthesie pour cesarienne. Acquisition des donnees Revue de la litterature. Recueil de donnees a partir de la base Medline, concernant l'hypotension arterielle au cours de la rachianesthesie pour cesarienne. Les articles publies en anglais ou en francais ont ete analyses. Synthese des donnees L'hypotension arterielle au cours de la rachianesthesie pour cesarienne est tres frequente (55 a 90 %) si elle n'est pas prevenue. Elle peut avoir des consequences nefastes pour la mere et le fœtus. Le preremplissage par cristalloide est inefficace. Le preremplissage par colloide est efficace mais plutot indique en deuxieme intention. L'ephedrine a longtemps represente le vasopresseur de reference. Cependant, sa faible efficacite en prophylaxie et ses effets cardiovasculaires maternels ainsi que sur le pH arteriel ombilical ont remis en question son utilisation, notamment au-dela de 15 a 20 mg. La phenylephrine, agent alpha-agoniste pur, en association ou non avec l'ephedrine selon la frequence cardiaque maternelle, a une efficacite au moins equivalente, voire superieure en prophylaxie et moins d'effets secondaires que l'ephedrine seule. Un co-/post-remplissage par cristalloide au moment de l'injection intrathecale ameliore le controle hemodynamique obtenu avec les vasopresseurs. Conclusion L'hypotension arterielle au cours de la rachianesthesie pour cesarienne doit systematiquement etre recherchee, prevenue et traitee sans delai. L'association de vasopresseur(s) (phenylephrine ± ephedrine) avec un remplissage rapide par cristalloide au moment de l'injection intrathecale represente la strategie la plus interessante actuellement.
- Published
- 2007
43. Doxazosin for the Management of Distal-Ureteral Stones
- Author
-
E.N. Liatsikos, Jens-Uwe Stolzenburg, Panagiotis Kallidonis, Anastasios Athanasopoulos, Petros Perimenis, T. Voudoukis, Paraskevi F. Katsakiori, Konstantinos Assimakopoulos, and Costantinos Constantinides
- Subjects
Adult ,Male ,Nephrology ,medicine.medical_specialty ,Ureteral Calculi ,Colic ,Urology ,Urinary stone ,Treatment outcome ,urologic and male genital diseases ,α1 adrenergic receptor ,Internal medicine ,medicine ,Doxazosin ,Humans ,Adrenergic alpha-Antagonists ,Models, Statistical ,Doxazosine ,business.industry ,Middle Aged ,Distal ureter ,Doxazosina ,Surgery ,Treatment Outcome ,Sample Size ,Female ,business ,medicine.drug - Abstract
To evaluate the efficacy of doxazosin in inducing spontaneous passage of stones in the distal ureter and to compare its efficacy according to the size of the stone.Seventy-three patients with a mean age of 46.38 +/- 10.17 years who presented with a distal-ureteral stone were divided into four groups according to stone size and drug treatment:5 mm without doxazosin (group A; n=15); 5-10 mm (group B; n=16);5 mm with doxazosin 4 mg/day for 4 weeks (group C; n=20); and 5-10 mm with doxazosin 4 mg/day for 4 weeks (group D; n=22). Groups A and B served as controls for groups C and D, respectively.Spontaneous stone passage was documented in 9 patients (60%) in group A v 17 (85%) in group C (P=0.047) and 7 (43.75%) in group B v 16 (72.73%) in group D (P=0.036). The average expulsion time was 8.78 +/- 1.09 days in group A v 7.59 +/- 0.80 days in group C (P=0.004) and 12.14 +/- 1.35 days in group B v 7.06 +/- 1.29 days in group D (P0.0001). The number of pain episodes in group D patients was significantly lower than in group B (P +/- 0.0078).Doxazosin treatment proved to be safe and effective for distal-ureteral stones, as determined by earlier expulsion, decreased colic frequency, and absence of side effects. The efficacy of doxazosin was significantly higher for 5-to 10-mm stones than for smaller ones.
- Published
- 2007
44. Cardiovascular Pharmacological Characteristics of S-2150: A Novel Dual Blocker of Calcium Channels and α1-Adrenoceptors
- Author
-
Mitsuyoshi Nakashima, Kazumi Iwaki, and Morio Kishi
- Subjects
Pharmacology ,Cardioprotection ,medicine.medical_specialty ,Voltage-dependent calcium channel ,Chemistry ,medicine.drug_class ,Antagonist ,Biological activity ,Calcium channel blocker ,Benzothiazepine derivatives ,α1 adrenergic receptor ,α1 adrenoceptor ,Endocrinology ,Internal medicine ,medicine ,Cardiology and Cardiovascular Medicine - Published
- 2007
45. Therapeutic Applications of Agents Interacting with the �-Adrenoceptor
- Author
-
Robert R. Rujfolo and J. Paul Hieble
- Subjects
Agonist ,medicine.medical_specialty ,α2 adrenergic receptor ,medicine.drug_class ,business.industry ,Pharmacology ,α1 adrenergic receptor ,Coronary heart disease ,β adrenoceptor ,Endocrinology ,Internal medicine ,medicine ,β adrenergic receptor ,business - Published
- 2015
46. a-Adrenoceptor Subclassification
- Author
-
Robert R. Ruffolo and Andrew J. Nichols
- Subjects
Nervous system ,medicine.medical_specialty ,medicine.anatomical_structure ,α2 adrenergic receptor ,Endocrinology ,Chemistry ,Internal medicine ,medicine ,Catecholamine ,α1 adrenergic receptor ,medicine.drug - Published
- 2015
47. Phosphorylation of the Na + ‐H + Exchanger Isoform 1 Initiated by α 1 ‐Adrenergic Receptor Signaling Regulates Cell Growth and Movement
- Author
-
Anne Pius, Ashley Wood, Joseph J. Provost, and Mark A. Wallert
- Subjects
Gene isoform ,Cell growth ,Chemistry ,Cancer ,Cell migration ,Stimulation ,medicine.disease ,Biochemistry ,α1 adrenergic receptor ,Cell biology ,Sodium–hydrogen antiporter ,Genetics ,medicine ,Phosphorylation ,Molecular Biology ,Biotechnology - Abstract
α1-adrenergic receptor signaling has been implicated in cancer progression through the stimulation of cell proliferation, cell migration and cell invasion. Conversely, blocking α1-adrenergic recept...
- Published
- 2015
48. Mydriase préopératoire obtenue par insert ophtalmique versus collyres
- Author
-
N. Limelette, Alain Gaudric, J. Oliary, Ramin Tadayoni, T. Caruba, and C. Couffon-Partant
- Subjects
Gynecology ,Ophthalmology ,medicine.medical_specialty ,Ophthalmic solutions ,business.industry ,Tropicamida ,Medicine ,Delivery system ,business ,α1 adrenergic receptor - Abstract
Objectifs L’objectif principal etait de determiner si la qualite de la mydriase preoperatoire obtenue avec un protocole de dilatation utilisant un insert etait au moins egale a celle obtenue avec un protocole utilisant exclusivement des collyres. Les objectifs secondaires etaient d’evaluer la tolerance locale et la facilite d’utilisation. Patients et methodes Nous avons mene une etude prospective randomisee, controlee, dans le service d’Ophtalmologie de l’Hopital Lariboisiere sur une periode de 3 semaines. Les 51 patients inclus ont ete repartis en deux groupes : 25 dans le groupe insert (atropine 1 %, diclofenac 0,1 % collyres et Mydriasert ® ) et 26 dans le groupe collyres (atropine 1 %, diclofenac 0,1 %, tropicamide 0,5 % et phenylephrine 10 % collyres). L’intensite de la mydriase a ete evaluee par une infirmiere et un chirurgien. La facilite d’utilisation a ete evaluee par le nombre de gestes infirmiers necessaires a l’obtention de la mydriase. La tolerance a ete appreciee par interrogatoire du patient. Resultats Une mydriase superieure a 6 mm a ete obtenue chez 92 % des patients du groupe insert (23/25) et 85 % des patients du groupe collyres (22/26) (difference non significative). Quatre patients ont perdu leur insert en cours de protocole. Respectivement 16 % (4/25) et 23 % (6/26) des patients des groupes insert et collyres ont rapporte des picotements (difference non significative). Le protocole avec insert a necessite cinq gestes infirmiers de moins par patient pour obtenir une mydriase satisfaisante (p Conclusions Le protocole de dilatation utilisant un insert permet d’obtenir une mydriase preoperatoire non inferieure a celle obtenue avec un protocole utilisant exclusivement des collyres, tout en permettant un gain de temps infirmier. Une formation des infirmieres a la pose de l’insert est indispensable afin d’eviter la perte du dispositif.
- Published
- 2006
49. Role of α1-Adrenoceptors of the Locus Coeruleus in Self-Stimulation of the Medial Forebrain Bundle
- Author
-
Eric A. Stone, Soledad Cabeza de Vaca, Kenneth D. Carr, and Yan Lin
- Subjects
Male ,endocrine system ,medicine.medical_specialty ,Adrenergic receptor ,Central nervous system ,Self Administration ,Stimulation ,α1 adrenergic receptor ,Rats, Sprague-Dawley ,Phenylephrine ,Receptors, Adrenergic, alpha-1 ,Internal medicine ,Animals ,Medicine ,Medial forebrain bundle ,Adrenergic alpha-Antagonists ,Pharmacology ,Behavior, Animal ,Dose-Response Relationship, Drug ,business.industry ,musculoskeletal, neural, and ocular physiology ,Medial Forebrain Bundle ,Prazosin ,α1 adrenoceptor ,Electric Stimulation ,Rats ,Psychiatry and Mental health ,Endocrinology ,medicine.anatomical_structure ,nervous system ,behavior and behavior mechanisms ,Locus coeruleus ,Locus Coeruleus ,business ,Adrenergic alpha-Agonists ,Neuroscience ,psychological phenomena and processes - Abstract
The present experiments were undertaken to clarify the role of central alpha(1)-adrenoceptors in reward processes. Rats, trained to self-stimulate via electrodes in the medial forebrain bundle of the lateral hypothalamus, were administered alpha(1)-selective drugs near the locus coeruleus (LC), a site of a dense concentration of alpha(1)-receptors. Effects on reward potency were assessed from shifts in rate-frequency curves while effects on motor response capacity were judged from changes in the maximal rates of responding. It was found that local blockade of LC alpha(1)-receptors with terazosin produced a significant dose-dependent and site-dependent rightward shift of 0.08 log units and a significant decrease of 16.3% in the maximum response rate. Both effects were completely reversed by coadministration of the alpha(1)-agonist, phenylephrine and were not attributable to terazosin's weak action at alpha(2)-adrenoceptors. It is concluded that LC alpha(1)-adrenoceptors are involved both in reward/motivational processes and operant response elaboration which are postulated to work together to facilitate goal attainment.
- Published
- 2006
50. alpha1-Adrenoceptor subtypes in isolated corporal tissue from patients undergoing gender re-assignment
- Author
-
Ruth A. Elliott, D. P. S. Sandhu, Tim R. Terry, and Osama M. El-Gamal
- Subjects
Nephrology ,medicine.medical_specialty ,Adrenergic receptor ,business.industry ,Urology ,Urinary system ,α1 adrenergic receptor ,α1 adrenoceptor ,medicine.anatomical_structure ,Endocrinology ,Internal medicine ,medicine ,business ,Penis - Abstract
This paper was published as BJU International, 2006, 97 (2), pp. 329-332. It is available from http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1464-410X. Doi: 10.1111/j.1464-410X.2006.05956.x
- Published
- 2006
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