320 results on '"Vanilloids"'
Search Results
2. Eugenol and Other Vanilloids Hamper Caenorhabditis elegans Response to Noxious Heat.
- Author
-
Nkambeu, Bruno, Ben Salem, Jennifer, and Beaudry, Francis
- Subjects
- *
CAENORHABDITIS elegans , *CAENORHABDITIS , *EUGENOL , *TRPV cation channels , *STRUCTURE-activity relationships , *FRONTIER orbitals , *TRP channels - Abstract
Eugenol, a known vanilloid, was frequently used in dentistry as a local analgesic in addition, antibacterial and neuroprotective effects were also reported. Eugenol, capsaicin and many vanilloids are interacting with the transient receptor potential vanilloid 1 (TRPV1) in mammals and the TRPV1 is activated by noxious heat. The pharmacological manipulation of the TRPV1 has been shown to have therapeutic value. Caenorhabditis elegans (C. elegans) express TRPV orthologs (e.g. OCR-2, OSM-9) and it is a commonly used animal model system to study nociception as it displays a well-defined and reproducible nocifensive behavior. After exposure to vanilloid solutions, C. elegans wild type (N2) and mutants were placed on petri dishes divided in quadrants for heat stimulation. Thermal avoidance index was used to phenotype each tested C. elegans experimental groups. The results showed that eugenol, vanillin and zingerone can hamper nocifensive response of C. elegans to noxious heat (32–35 °C) following a sustained exposition. Also, the effect was reversed 6 h post exposition. Furthermore, eugenol and vanillin did not target specifically the OCR-2 or OSM-9 but zingerone did specifically target the OCR-2 similarly to capsaicin. Further structural and physicochemical analyses were performed. Key parameters for quantitative structure-property relationships (QSPR), quantitative structure-activity relationships (QSAR) and frontier orbital analyses suggest similarities and dissimilarities amongst the tested vanilloids and capsaicin in accordance with the relative anti-nociceptive effects observed. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
3. TRPV1 Ion Channel: Structural Features, Activity Modulators, and Therapeutic Potential.
- Author
-
Gladkikh, Irina N., Sintsova, Oksana V., Leychenko, Elena V., and Kozlov, Sergey A.
- Abstract
Although TRPV1 ion channel has been attracting researchers' attention for many years, its functions in animal organisms, the principles of regulation, and the involvement in pathological processes have not yet been fully clarified. Mutagenesis experiments and structural studies have identified the structural features of the channel and binding sites for its numerous ligands; however, these studies are far from conclusion. This review summarizes recent achievements in the TRPV1 research with special focus on structural and functional studies of the channel and on its ligands, which are extremely diverse in their nature and interaction specificity to TRPV1. Particular attention was given to the effects of numerous endogenous agonists and antagonists that can fine-tune the channel sensitivity to its usual activators, such as capsaicin, heat, acids, or their combination. In addition to the pain sensing not covered in this review, the TRPV1 channel was found to be involved in the regulation of many important physiological and pathological processes and, therefore, can be considered as a promising therapeutic target in the treatment of various diseases, such as pneumonia, ischemia, diabetes, epilepsy, schizophrenia, psoriasis, etc. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
4. High-Content Screening Identifies Vanilloids as a Novel Class of Inhibitors of NET Formation
- Author
-
Elvira Sondo, Roberta Bertelli, Emanuela Pesce, Gian Marco Ghiggeri, and Nicoletta Pedemonte
- Subjects
NETosis ,high-content screening ,vanilloids ,NETs ,inhibitors ,neutrophil ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Neutrophils migrate to sites of infection where they phagocytose, degranulate, and/or, in the presence of appropriate stimuli, release decondensed chromatin strands (called neutrophil extracellular traps, NETs) for trapping and possibly killing microorganisms. NET formation is characterized by marked morphological cell changes, in particular within the nucleus. Lytic NET formation can be observed in neutrophils undergoing cell death, which is referred to as NETosis. Dysregulation of NET production and/or degradation can exert pathogenic effects, contributing to the pathogenesis of various diseases, including cystic fibrosis, autoimmune diseases and inflammatory conditions. By employing a phenotypic assay based on high-content imaging and analysis, we screened a library of biologically active compounds and identified vanilloids as a novel class of chemical compounds able to hinder NETosis induction and NET release. Vanilloids also markedly decrease cytosolic ROS production. The identification of novel vanilloid NET inhibitors, able to stop excessive or aberrant NET production might offer new therapeutic options for those disorders displaying NET overproduction.
- Published
- 2019
- Full Text
- View/download PDF
5. Interplay between endocannabinoid and endovanilloid mechanisms in fear conditioning.
- Author
-
Briânis RC, Andreotti JP, Moreira FA, and Iglesias LP
- Abstract
Objective: The transient receptor potential cation channel, subfamily V (vanilloid), member 1 (TRPV1) mediates pain perception to thermal and chemical stimuli in peripheral neurons. The cannabinoid receptor type 1 (CB
1 ), on the other hand, promotes analgesia in both the periphery and the brain. TRPV1 and CB1 have also been implicated in learned fear, which involves the association of a previously neutral stimulus with an aversive event. In this review, we elaborate on the interplay between CB1 receptors and TRPV1 channels in learned fear processing., Methods: We conducted a PubMed search for a narrative review on endocannabinoid and endovanilloid mechanisms on fear conditioning., Results: TRPV1 and CB1 receptors are activated by a common endogenous agonist, arachidonoyl ethanolamide (anandamide), Moreover, they are expressed in common neuroanatomical structures and recruit converging cellular pathways, acting in concert to modulate fear learning. However, evidence suggests that TRPV1 exerts a facilitatory role, whereas CB1 restrains fear responses., Conclusion: TRPV1 and CB1 seem to mediate protective and aversive roles of anandamide, respectively. However, more research is needed to achieve a better understanding of how these receptors interact to modulate fear learning.- Published
- 2023
- Full Text
- View/download PDF
6. TRPV1 Activators ('Vanilloids') as Neurotoxins
- Author
-
Kumar, Ashutosh, Majhi, Rakesh Kumar, Yadav, Manoj, Szallasi, Arpad, Goswami, Chandan, and Kostrzewa, Richard M., editor
- Published
- 2014
- Full Text
- View/download PDF
7. Survey of Selective Neurotoxins
- Author
-
Kostrzewa, Richard M. and Kostrzewa, Richard M., editor
- Published
- 2014
- Full Text
- View/download PDF
8. High-Content Screening Identifies Vanilloids as a Novel Class of Inhibitors of NET Formation.
- Author
-
Sondo, Elvira, Bertelli, Roberta, Pesce, Emanuela, Ghiggeri, Gian Marco, and Pedemonte, Nicoletta
- Subjects
NEUTROPHILS ,CELL death ,CYSTIC fibrosis ,AUTOIMMUNE diseases ,INFLAMMATION - Abstract
Neutrophils migrate to sites of infection where they phagocytose, degranulate, and/or, in the presence of appropriate stimuli, release decondensed chromatin strands (called neutrophil extracellular traps, NETs) for trapping and possibly killing microorganisms. NET formation is characterized by marked morphological cell changes, in particular within the nucleus. Lytic NET formation can be observed in neutrophils undergoing cell death, which is referred to as NETosis. Dysregulation of NET production and/or degradation can exert pathogenic effects, contributing to the pathogenesis of various diseases, including cystic fibrosis, autoimmune diseases and inflammatory conditions. By employing a phenotypic assay based on high-content imaging and analysis, we screened a library of biologically active compounds and identified vanilloids as a novel class of chemical compounds able to hinder NETosis induction and NET release. Vanilloids also markedly decrease cytosolic ROS production. The identification of novel vanilloid NET inhibitors, able to stop excessive or aberrant NET production might offer new therapeutic options for those disorders displaying NET overproduction. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
9. TRPV1 antagonists that cause hypothermia, instead of hyperthermia, in rodents: Compounds’ pharmacological profiles, in vivo targets, thermoeffectors recruited and implications for drug development.
- Author
-
Garami, A., Pakai, E., McDonald, H. A., Reilly, R. M., Gomtsyan, A., Corrigan, J. J., Pinter, E., Zhu, D. X. D., Lehto, S. G., Gavva, N. R., Kym, P. R., and Romanovsky, A. A.
- Subjects
- *
TRPV cation channels , *HYPOTHERMIA , *FEVER , *LABORATORY rats , *LABORATORY mice - Abstract
Abstract: Aim: Thermoregulatory side effects hinder the development of transient receptor potential vanilloid‐1 (TRPV1) antagonists as new painkillers. While many antagonists cause hyperthermia, a well‐studied effect, some cause hypothermia. The mechanisms of this hypothermia are unknown and were studied herein. Methods: Two hypothermia‐inducing TRPV1 antagonists, the newly synthesized A‐1165901 and the known AMG7905, were used in physiological experiments in rats and mice. Their pharmacological profiles against rat TRPV1 were studied in vitro. Results: Administered peripherally, A‐1165901 caused hypothermia in rats by either triggering tail‐skin vasodilation (at thermoneutrality) or inhibiting thermogenesis (in the cold). A‐1165901‐induced hypothermia did not occur in rats with desensitized (by an intraperitoneal dose of the TRPV1 agonist resiniferatoxin) sensory abdominal nerves. The hypothermic responses to A‐1165901 and AMG7905 (administered intragastrically or intraperitoneally) were absent in Trpv1−/− mice, even though both compounds evoked pronounced hypothermia in Trpv1+/+ mice. In vitro, both A‐1165901 and AMG7905 potently potentiated TRPV1 activation by protons, while potently blocking channel activation by capsaicin. Conclusion: TRPV1 antagonists cause hypothermia by an on‐target action: on TRPV1 channels on abdominal sensory nerves. These channels are tonically activated by protons and drive the reflectory inhibition of thermogenesis and tail‐skin vasoconstriction. Those TRPV1 antagonists that cause hypothermia further inhibit these cold defences, thus decreasing body temperature. Significance: TRPV1 antagonists (of capsaicin activation) are highly unusual in that they can cause both hyper‐ and hypothermia by modulating the same mechanism. For drug development, this means that both side effects can be dealt with simultaneously, by minimizing these compounds’ interference with TRPV1 activation by protons. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
10. Drug-like dietary vanilloids induce anticancer activity through proliferation inhibition and regulation of bcl-related apoptotic proteins.
- Author
-
Mai, Chun‐Wai, Kang, Yew‐Beng, Nadarajah, Vishna Devi, Hamzah, Ahmad Sazali, Pichika, Mallikarjuna Rao, Mai, Chun-Wai, and Kang, Yew-Beng
- Subjects
PROTEIN metabolism ,ANTINEOPLASTIC agents ,APOPTOSIS ,BIOLOGICAL models ,CARRIER proteins ,CELL lines ,CELL physiology ,MOLECULAR structure ,IN vitro studies ,PHARMACODYNAMICS ,THERAPEUTICS - Abstract
In this study, a series of 20 structurally similar vanilloids (Vn) were tested for their antiproliferative effects against 12 human cancer cells: human breast (MCF-7 and MDA-MB-231), cervical (HeLa), ovarian (Caov-3), lung (A549), liver (HepG2), colorectal (HT-29 and HCT116), nasopharyngeal (CNE-1 and HK-1), and leukemic (K562 and CEM-SS) cancer cells. Among all the tested vanilloids, Vn16 (6-shogaol) exhibited the most potent cytotoxic effects against human colorectal cancer cells (HT-29). The apoptotic induction effects exhibited by Vn16 on HT-29 cells were confirmed using dual staining fluorescence microscopy and enzyme-linked immunosorbent assay. The effects of Vn16 on regulation of 43 apoptotic-related markers were determined in HT-29. The results suggested that 8 apoptotic markers (caspase 8, BAD, BAX, second mitochondrial-derived activator, caspase 3, survivin, bcl-2, and cIAP-2) were either upregulated or downregulated. These results further support the chemopreventive properties of foods that contain vanilloids. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
11. Intravesical vanilloids for treating neurogenic lower urinary tract dysfunction in patients with multiple sclerosis: A systematic review and meta‐analysis. A report from the Neuro‐Urology Promotion Committee of the International Continence Society (ICS)
- Author
-
Phé, Véronique, Schneider, Marc P., Peyronnet, Benoit, Abo Youssef, Nadim, Mordasini, Livio, Chartier‐Kastler, Emmanuel, Bachmann, Lucas M., and Kessler, Thomas M.
- Abstract
Aims: To systematically assess all available evidence on efficacy and safety of vanilloids for treating neurogenic lower urinary tract dysfunction (NLUTD) in patients with multiple sclerosis (MS). Methods: This systematic review and meta‐analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement. Studies were identified by electronic search of Cochrane register, Embase, Medline, Scopus, (last search January 8, 2016). Results: After screening of 7848 abstracts, 4 randomized controlled trials (RCTs) and 3 prospective cohort studies were included. Pooled data from three RCTs evaluating intravesical capsaicin showed the standardized mean difference to be −2.16 (95% confidence interval [CI] −2.87 to −1.45) in incontinence episodes per 24 h and −0.54 (95%CI −1.03 to −0.05) in voids per 24 h. There was no statistically significant effect on maximum cystometric capacity and maximum storage detrusor pressure. Overall, adverse events were reported by >50% of the patients, most commonly were pelvic pain, facial flush, worsening of incontinence, autonomic dysreflexia, urinary tract infection and haematuria. Risk of bias and confounding was relevant in both RCTs and non‐RCTs. Conclusions: Preliminary data suggest that intravesical vanilloids might be effective for treating NLUTD in patients with MS. However, the safety profile seems unfavorable, the overall quality of evidence is low and no licensed substance is currently available warranting well‐designed, adequately sampled and properly powered RCTs. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
12. Spontaneous and Bite-Evoked Muscle Pain Are Mediated by a Common Nociceptive Pathway With Differential Contribution by TRPV1.
- Author
-
Wang, Sheng, Lim, Jongseuk, Joseph, John, Wang, Sen, Wei, Feng, Ro, Jin Y., and Chung, Man-Kyo
- Abstract
Spontaneous pain and function-associated pain are prevalent symptoms of multiple acute and chronic muscle pathologies. We established mouse models for evaluating spontaneous pain and bite-evoked pain from masseter muscle, and determined the roles of transient receptor potential cation channel subfamily V member 1 (TRPV1) and the contribution of TRPV1- or neurokinin 1 (NK1)-dependent nociceptive pathways. Masseter muscle inflammation increased Mouse Grimace Scale scores and face-wiping behavior, which were attenuated by pharmacological or genetic inhibition of TRPV1. Masseter inflammation led to a significant reduction in bite force. Inhibition of TRPV1 only marginally relieved the inflammation-induced reduction of bite force. These results suggest a differential extent of contribution of TRPV1 to the 2 types of muscle pain. However, chemical ablation of TRPV1-expressing nociceptors or chemogenetic silencing of TRPV1-lineage nerve terminals in masseter muscle attenuated inflammation-induced changes in Mouse Grimace Scale scores as well as bite force. Furthermore, ablation of neurons expressing NK1 receptor in trigeminal subnucleus caudalis also prevented both types of muscle pain. Our results suggest that TRPV1 differentially contributes to spontaneous pain and bite-evoked muscle pain, but TRPV1-expressing afferents and NK1-expressing second-order neurons commonly mediate both types of muscle pain. Therefore, manipulation of the nociceptive circuit may provide a novel approach for management of acute or chronic craniofacial muscle pain.
Perspective: We report the profound contribution of TRPV1 to spontaneous muscle pain but not to bite-evoked muscle pain. These 2 types of muscle pain are transmitted through a common nociceptive pathway. These results may help to develop new strategies to manage multiple modes of muscle pain simultaneously by manipulating pain circuits. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
13. Cannabinoids and Vanilloids in Schizophrenia: Neurophysiological Evidence and Directions for Basic Research
- Author
-
Rafael N. Ruggiero, Matheus T. Rossignoli, Jana B. De Ross, Jaime E. C. Hallak, Joao P. Leite, and Lezio S. Bueno-Junior
- Subjects
cannabinoids ,vanilloids ,schizophrenia ,functional imaging ,electrophysiology ,animal models ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Much of our knowledge of the endocannabinoid system in schizophrenia comes from behavioral measures in rodents, like prepulse inhibition of the acoustic startle and open-field locomotion, which are commonly used along with neurochemical approaches or drug challenge designs. Such methods continue to map fundamental mechanisms of sensorimotor gating, hyperlocomotion, social interaction, and underlying monoaminergic, glutamatergic, and GABAergic disturbances. These strategies will require, however, a greater use of neurophysiological tools to better inform clinical research. In this sense, electrophysiology and viral vector-based circuit dissection, like optogenetics, can further elucidate how exogenous cannabinoids worsen (e.g., tetrahydrocannabinol, THC) or ameliorate (e.g., cannabidiol, CBD) schizophrenia symptoms, like hallucinations, delusions, and cognitive deficits. Also, recent studies point to a complex endocannabinoid-endovanilloid interplay, including the influence of anandamide (endogenous CB1 and TRPV1 agonist) on cognitive variables, such as aversive memory extinction. In fact, growing interest has been devoted to TRPV1 receptors as promising therapeutic targets. Here, these issues are reviewed with an emphasis on the neurophysiological evidence. First, we contextualize imaging and electrographic findings in humans. Then, we present a comprehensive review on rodent electrophysiology. Finally, we discuss how basic research will benefit from further combining psychopharmacological and neurophysiological tools.
- Published
- 2017
- Full Text
- View/download PDF
14. Molecular Surgery Concept from Bench to Bedside: A Focus on TRPV1+ Pain-Sensing Neurons
- Author
-
László Pecze, Béla Viskolcz, and Zoltán Oláh
- Subjects
TRPV1 ,vanilloids ,capsaicin ,resiniferatoxin ,sensory neurons ,necrosis ,Physiology ,QP1-981 - Abstract
“Molecular neurosurgery” is emerging as a new medical concept, and is the combination of two partners: (i) a molecular neurosurgery agent, and (ii) the cognate receptor whose activation results in the selective elimination of a specific subset of neurons in which this receptor is endogenously expressed. In general, a molecular surgery agent is a selective and potent ligand, and the target is a specific cell type whose elimination is desired through the molecular surgery procedure. These target cells have the highest innate sensitivity to the molecular surgery agent usually due to the highest receptor density being in their plasma membrane. The interaction between the ligand and its receptor evokes an overactivity of the receptor. If the receptor is a ligand-activated non-selective cation channel, the overactivity of receptor leads to excess Ca2+ and Na+ influx into the cell and finally cell death. One of the best known examples of such an interaction is the effect of ultrapotent vanilloids on TRPV1-expressing pain-sensing neurons. One intrathecal resiniferatoxin (RTX) dose allows for the receptor-mediated removal of TRPV1+ neurons from the peripheral nervous system. The TRPV1 receptor-mediated ion influx induces necrotic processes, but only in pain-sensing neurons, and usually within an hour. Besides that, target-specific apoptotic processes are also induced. Thus, as a nano-surgery scalpel, RTX removes the neurons responsible for generating pain and inflammation from the peripheral nervous system providing an option in clinical management for the treatment of morphine-insensitive pain conditions. In the future, the molecular surgery concept can also be exploited in cancer research for selectively targeting the specific tumor cell.
- Published
- 2017
- Full Text
- View/download PDF
15. TRPV2 channel-based therapies in the cardiovascular field. Molecular underpinnings of clinically relevant therapies
- Author
-
Nathan Robbins, Jack Rubinstein, Brian O’Connor, and Sheryl E. Koch
- Subjects
030303 biophysics ,TRPV2 ,Biophysics ,TRPV1 ,Cardiomyopathy ,TRPV Cation Channels ,Bioinformatics ,Cardiovascular System ,TRPV ,Muscular Dystrophies ,Vanilloids ,03 medical and health sciences ,Transient receptor potential channel ,chemistry.chemical_compound ,Mediator ,Drug Discovery ,Animals ,Humans ,Medicine ,Myocytes, Cardiac ,Molecular Biology ,Heart Failure ,Clinical Trials as Topic ,0303 health sciences ,business.industry ,Heart ,medicine.disease ,Biomechanical Phenomena ,Disease Models, Animal ,chemistry ,Calcium ,Translational science ,Cardiomyopathies ,business ,Signal Transduction - Abstract
The transient receptor potential (TRP) ion channel family is composed of twenty-seven channel proteins that are ubiquitously expressed in the human body. The TRPV (vanilloid) subfamily has been a recent target of investigation within the cardiovascular field. TRPV1, which is sensitive to heat as well as vanilloids, is the best characterized TRPV channel and is the namesake for the subfamily that includes six members. Research into the function of TRPV2 has suggested that it plays an important role in cardiovascular function. Over the last twenty years a greater understanding of the differences among the TRPV channels has allowed for more precise experimentation and has opened various translational opportunities. TRPV2 has been found to be a both a mechanosensor and a mediator of calcium handling and has been found to play important roles in healthy and diseased cardiomyocytes. These roles have been translated into clinical studies in patients with muscular dystrophy (both agonism and antagonism) as well as in patients with cardiomyopathy and heart failure with reduced ejection fraction. Its role as a structural protein has also been elucidated, though the clinical significance of this finding has yet to be established. Despite the clinical progress that has been made there is still a need for large, prospective randomized studies with TRPV2 channel agonists and antagonists in order to bring these basic and translational science findings to the bedside.
- Published
- 2021
16. Eugenol and Other Vanilloids Hamper Caenorhabditis elegans Response to Noxious Heat
- Author
-
Jennifer Ben Salem, Bruno Nkambeu, Francis Beaudry, and Université de Montréal. Faculté de médecine vétérinaire
- Subjects
Nociception ,0301 basic medicine ,Zingerone ,TRPV1 ,Pharmacology ,Biochemistry ,TRPV ,Vanilloids ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Transient receptor potential channel ,0302 clinical medicine ,Eugenol ,Caenorhabditis elegans ,biology ,General Medicine ,biology.organism_classification ,Transient receptor potential cation channel ,3. Good health ,030104 developmental biology ,chemistry ,Capsaicin ,Vanillin ,lipids (amino acids, peptides, and proteins) ,030217 neurology & neurosurgery - Abstract
Eugenol, a known vanilloid, was frequently used in dentistry as a local analgesic in addition, antibacterial and neuroprotective effects were also reported. Eugenol, capsaicin and many vanilloids are interacting with the transient receptor potential vanilloid 1 (TRPV1) in mammals and the TRPV1 is activated by noxious heat. The pharmacological manipulation of the TRPV1 has been shown to have therapeutic value. Caenorhabditis elegans (C. elegans) express TRPV orthologs (e.g. OCR-2, OSM-9) and it is a commonly used animal model system to study nociception as it displays a well-defined and reproducible nocifensive behavior. After exposure to vanilloid solutions, C. elegans wild type (N2) and mutants were placed on petri dishes divided in quadrants for heat stimulation. Thermal avoidance index was used to phenotype each tested C. elegans experimental groups. The results showed that eugenol, vanillin and zingerone can hamper nocifensive response of C. elegans to noxious heat (32-35 °C) following a sustained exposition. Also, the effect was reversed 6 h post exposition. Furthermore, eugenol and vanillin did not target specifically the OCR-2 or OSM-9 but zingerone did specifically target the OCR-2 similarly to capsaicin. Further structural and physicochemical analyses were performed. Key parameters for quantitative structure-property relationships (QSPR), quantitative structure-activity relationships (QSAR) and frontier orbital analyses suggest similarities and dissimilarities amongst the tested vanilloids and capsaicin in accordance with the relative anti-nociceptive effects observed.
- Published
- 2020
17. Cannabinoids and Vanilloids in Schizophrenia: Neurophysiological Evidence and Directions for Basic Research.
- Author
-
Ruggiero, Rafael N., Rossignoli, Matheus T., De Ross, Jana B., Hallak, Jaime E. C., Leite, Joao P., and Bueno-Junior, Lezio S.
- Subjects
CANNABINOIDS ,SCHIZOPHRENIA ,NEUROPHYSIOLOGY - Abstract
Much of our knowledge of the endocannabinoid system in schizophrenia comes from behavioral measures in rodents, like prepulse inhibition of the acoustic startle and open-field locomotion, which are commonly used along with neurochemical approaches or drug challenge designs. Such methods continue to map fundamental mechanisms of sensorimotor gating, hyperlocomotion, social interaction, and underlying monoaminergic, glutamatergic, and GABAergic disturbances. These strategies will require, however, a greater use of neurophysiological tools to better inform clinical research. In this sense, electrophysiology and viral vector-based circuit dissection, like optogenetics, can further elucidate how exogenous cannabinoids worsen (e.g., tetrahydrocannabinol, THC) or ameliorate (e.g., cannabidiol, CBD) schizophrenia symptoms, like hallucinations, delusions, and cognitive deficits. Also, recent studies point to a complex endocannabinoid-endovanilloid interplay, including the influence of anandamide (endogenous CB
1 and TRPV1 agonist) on cognitive variables, such as aversive memory extinction. In fact, growing interest has been devoted to TRPV1 receptors as promising therapeutic targets. Here, these issues are reviewed with an emphasis on the neurophysiological evidence. First, we contextualize imaging and electrographic findings in humans. Then, we present a comprehensive review on rodent electrophysiology. Finally, we discuss how basic research will benefit from further combining psychopharmacological and neurophysiological tools. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
18. Molecular Surgery Concept from Bench to Bedside: A Focus on TRPV1+ Pain-Sensing Neurons.
- Author
-
Pecze, László, Viskolcz, Béla, and Oláh, Zoltán
- Subjects
NEUROSURGERY ,CAPSAICIN ,RESINIFERATOXIN ,SENSORY neurons ,NECROSIS - Abstract
"Molecular neurosurgery" is emerging as a new medical concept, and is the combination of two partners: (i) a molecular neurosurgery agent, and (ii) the cognate receptor whose activation results in the selective elimination of a specific subset of neurons in which this receptor is endogenously expressed. In general, a molecular surgery agent is a selective and potent ligand, and the target is a specific cell type whose elimination is desired through the molecular surgery procedure. These target cells have the highest innate sensitivity to themolecular surgery agent usually due to the highest receptor density being in their plasma membrane. The interaction between the ligand and its receptor evokes an overactivity of the receptor. If the receptor is a ligand-activated non-selective cation channel, the overactivity of receptor leads to excess Ca
2+ and Na+ influx into the cell and finally cell death. One of the best known examples of such an interaction is the effect of ultrapotent vanilloids on TRPV1-expressing pain-sensing neurons. One intrathecal resiniferatoxin (RTX) dose allows for the receptor-mediated removal of TRPV1+ neurons from the peripheral nervous system. The TRPV1 receptor-mediated ion influx induces necrotic processes, but only in pain-sensing neurons, and usually within an hour. Besides that, target-specific apoptotic processes are also induced. Thus, as a nano-surgery scalpel, RTX removes the neurons responsible for generating pain and inflammation from the peripheral nervous system providing an option in clinical management for the treatment of morphine-insensitive pain conditions. In the future, the molecular surgery concept can also be exploited in cancer research for selectively targeting the specific tumor cell. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
19. Investigation of the effects of vanilloids in chronic fatigue syndrome.
- Author
-
Sarvaiya, Kuldeep and Goswami, Sunita
- Subjects
- *
CHRONIC fatigue syndrome treatment , *TRPV cation channels , *BIOCHEMICAL mechanism of action , *LACTATE dehydrogenase , *TREATMENT effectiveness - Abstract
Aim of the study To assess the effectiveness of TRPV1 modulators in animal model of Chronic fatigue syndrome (CFS). To assess central and peripheral behavioral activity of TRPV1 modulators. Material and methods CFS was induced by forcing the rats to swim for 10 min for 21 consecutive days. The rats were treated with capsaicin (TRPV1 agonist, 2.5 mg/kg) and n- tert -butylcyclohexanol (TRPV1 antagonist, 10 mg/kg) for 21 days 30 min before the exposure to stress procedure. The behavioral consequence of CFS was measured in terms of immobility time, grip strength, locomotor activity, and anxiety level using Rota rod, Actophotometer, and Elevated plus maze model respectively. The other parameters include Plasma corticosterone, adrenal gland and spleen weight, complete blood count, blood urea niterogen (BUN), Lactate dehydrogenase (LDH), Lipid peroxidation, catalase and reduced glutathione (GSH). Results and discussion TRPV1 modulators reversed (p < 0.05) the increase in immobility period, anxiety, spleen weight, BUN and LDH levels, and MDA levels along with decrease in grip strength, locomotor activity, plasma corticosterone, adrenal gland weight, catalase, and GSH. There was also significant increase in total WBC count when compared with the disease control group. The reversal was attributed to modulation of HPA axis, oxidative stress, anaerobic respiration product, muscle degradation product. Conclusion The present study reveals the effectiveness of n- tert -butylcyclohexanol and capsaicin against chronic fatigue syndrome. The mechanism of action can be attributed to inhibition of TRPV1 channel and thereby modulating pain perception, neuroendocrine function, oxidative stress and immune function. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
20. Fluorescence-Based Assay for TRPV1 Channels.
- Author
-
Moriello AS, De Petrocellis L, and Vitale RM
- Subjects
- Analgesics, Calcium metabolism, Capsaicin, Cations, Fluorescence, Fura-2, HEK293 Cells, Humans, Ligands, Pain drug therapy, TRPV Cation Channels physiology, Transient Receptor Potential Channels
- Abstract
The transient receptor potential vanilloid 1 ion channel (TRPV1) is a ligand-gated nonselective calcium-permeant cation channel involved in the detection of a wide variety of chemical and physical noxious stimuli, ranging from exogenous and endogenous ligands to noxious heat (>42 °C) and low pH (pH < 5.2). Due to its central role in pain and hyperalgesia, TRPV1 is considered a relevant therapeutic target for the development of analgesic and anti-inflammatory drugs potentially useful to relieve chronic, neuropathic, and inflammatory pain and to treat disorders such as inflammatory bowel disease. In this view, the availability of in vitro assays for the screening of novel TRPV1 modulators is highly desirable. Since TRPV1 activation leads to an increase in the intracellular calcium (Ca
2+ ) levels, the use of Ca2+ fluorescent indicators represent a valuable and sensitive tool for monitoring such intracellular changes. In this chapter, we describe methods for recording and monitoring Ca2+ signals through the fluorescent indicators Fluo-4 acetoxymethyl (AM) and Fura-2 AM in HEK-293 cells transfected with TRPV1 or other thermoTRP channels., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2023
- Full Text
- View/download PDF
21. Capsaicin, Nociception and Pain.
- Author
-
Frias, Bárbara and Merighi, Adalberto
- Abstract
Capsaicin, the pungent ingredient of the hot chili pepper, is known to act on the transient receptor potential cation channel vanilloid subfamily member 1 (TRPV1). TRPV1 is involved in somatic and visceral peripheral inflammation, in the modulation of nociceptive inputs to spinal cord and brain stem centers, as well as the integration of diverse painful stimuli. In this review, we first describe the chemical and pharmacological properties of capsaicin and its derivatives in relation to their analgesic properties. We then consider the biochemical and functional characteristics of TRPV1, focusing on its distribution and biological effects within the somatosensory and viscerosensory nociceptive systems. Finally, we discuss the use of capsaicin as an agonist of TRPV1 to model acute inflammation in slices and other ex vivo preparations. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
22. TRPV1 mediates capsaicin-stimulated metabolic activity but not cell death or inhibition of interleukin-1β release in human THP-1 monocytes
- Author
-
Dominic P. Geraghty, Januttha Yingchoncharoen, Dale Kunde, and Saša Jurković
- Subjects
0301 basic medicine ,Programmed cell death ,THP-1 Cells ,medicine.medical_treatment ,Interleukin-1beta ,Cell ,TRPV1 ,TRPV Cation Channels ,Pharmacology ,Toxicology ,Monocytes ,Vanilloids ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,Immune system ,medicine ,Humans ,THP1 cell line ,Cell Death ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Chemistry ,030104 developmental biology ,Cytokine ,medicine.anatomical_structure ,Capsaicin ,lipids (amino acids, peptides, and proteins) ,Diterpenes - Abstract
Human monocytes and dendritic cells express transient receptor potential vanilloid 1 (TRPV1) which may play a role in mediating the inflammatory, immune and cancer surveillance responses of these cells. The aim of the present study was to investigate TRPV1 expression and function in THP-1 monocytic cells. RT-PCR and Western blot were used to detect TRPV1. The metabolic activity and viability of THP-1 cells following exposure to vanilloids was assessed using resorufin production from rezazurin. Cytokine release was measured using ELISA. TRPV1 was expressed in cultured THP-1 monocytic cells and naïve monocytes. Lower concentrations (250 μM) of capsaicin, but not other putative TRPV1 agonists, were shown to stimulate cell metabolic activity, whereas at concentrations250 μM, all agonists decreased metabolic activity. Capsaicin-stimulated THP-1 metabolic activity was blocked by the TRPV1 antagonist, 5-iodo-resiniferatoxin (5'-IRTX), whereas the decline in resorufin production by THP-1 cells at higher capsaicin concentrations (due to cell death), was not affected by 5'-IRTX. Finally, capsaicin (≤125 μM) significantly increased lipopolysaccharide-stimulated IL-6 and TNF-α release from THP-1 cells, whereas phytohaemagglutinin-stimulated IL-1β, TNF-α, MCP-1 and IL-6 release were concentration-dependently inhibited by capsaicin. Modulation of IL-1β release was not TRPV1 mediated. Overall, these results show that functional TRPV1 channels are present in naïve monocytes and THP-1 cells, and when activated, increase cell metabolic activity. In addition, capsaicin modifies cytokine release from THP-1 cells and induces cell death, most likely by a mechanism that is independent of TRPV1 activation.
- Published
- 2018
23. 6-Paradol Acts as a Potential Anti-obesity Vanilloid from Grains of Paradise
- Author
-
Takahiro Shibata, Masaki Kita, Hiroyuki Hattori, Tohru Mitsunaga, and Takashi Mori
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Adipose tissue ,AMP-Activated Protein Kinases ,Weight Gain ,Vanilloids ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Zingiberaceae ,Internal medicine ,Adipocyte ,medicine ,Animals ,Obesity ,Protein kinase A ,Fatty acid synthesis ,030109 nutrition & dietetics ,Triglyceride ,Molecular Structure ,Plant Extracts ,Guaiacol ,AMPK ,Ketones ,030104 developmental biology ,Endocrinology ,chemistry ,Adipose Tissue ,Liver ,Seeds ,Paradol ,Anti-Obesity Agents ,Food Science ,Biotechnology - Abstract
Scope Grains of Paradise (GOP), the seeds of Aframomum melegueta, has anti-obesity effects. However, the mechanisms underlying the effects remain unclear. Methods and results We set up to study the anti-obesity impact and homeostatic effects of 6-paradol, a major vanilloid found in GOP, and investigated the physiological outputs and the lipometabolism-related gene in fat and liver in high-fat-induced obese mice with a comparison with structurally similar vanilloids (6-gingerol and 6-shogaol). The vanilloids were synthesized in adequate quantities for performing animal experiments and orally administered to six-week-old male mice over two weeks. We found that 6-paradol decreased body weight gain and visceral and subcutaneous fats in two weeks, whereas 6-gingerol and 6-shogaol had no effect. Additionally, 6-paradol suppressed the hepatic cholesterol and triglyceride and significantly decreased the gene expression related to fatty acid synthesis, lipid transportation, and adipocyte differentiation in both liver and adipose tissue. Moreover, phosphorylation of AMP-activated protein kinase (AMPK) that greatly contributes to lipometabolism was promoted by 6-gingerol but not 6-paradol. Conclusion These results suggest that 6-paradol regulates several obesity-related genes in an AMPK-independent manner. Therefore, it could be the principal active vanilloid in GOP giving it anti-obesity properties with a different mechanism. This article is protected by copyright. All rights reserved.
- Published
- 2021
24. Capsaicin, Nociception and Pain
- Author
-
Bárbara Frias and Adalberto Merighi
- Subjects
capsaicin ,vanilloids ,TRPV1 receptor ,nociception ,somatic pain ,visceral pain ,sensitization ,analgesia ,resinferatoxin ,Organic chemistry ,QD241-441 - Abstract
Capsaicin, the pungent ingredient of the hot chili pepper, is known to act on the transient receptor potential cation channel vanilloid subfamily member 1 (TRPV1). TRPV1 is involved in somatic and visceral peripheral inflammation, in the modulation of nociceptive inputs to spinal cord and brain stem centers, as well as the integration of diverse painful stimuli. In this review, we first describe the chemical and pharmacological properties of capsaicin and its derivatives in relation to their analgesic properties. We then consider the biochemical and functional characteristics of TRPV1, focusing on its distribution and biological effects within the somatosensory and viscerosensory nociceptive systems. Finally, we discuss the use of capsaicin as an agonist of TRPV1 to model acute inflammation in slices and other ex vivo preparations.
- Published
- 2016
- Full Text
- View/download PDF
25. Effect of chirality and lipophilicity in the functional activity of evodiamine and its analogues at TRPV1 channels.
- Author
-
De Petrocellis, Luciano, Schiano Moriello, Aniello, Fontana, Gabriele, Sacchetti, Alessandro, Passarella, Daniele, Appendino, Giovanni, and Di Marzo, Vincenzo
- Subjects
- *
CHIRALITY , *LIPOPHILICITY , *TRP channels , *TRPV cation channels , *TARTARIC acid , *CHINESE medicine , *BODY temperature regulation - Abstract
Background and Purpose Evodiamine, a racemic quinazolinocarboline alkaloid isolated from the traditional Chinese medicine Evodiae fructus, has been reported to act as an agonist of the transient receptor potential vanilloid type-1 ( TRPV1) cation channel both in vitro and in vivo. Evodiamine is structurally different from all known TRPV1 activators, and has significant clinical potential as a thermogenic agent. Nevertheless, the molecular bases for its actions are still poorly understood. Experimental Approach To investigate the structure-activity relationships of evodiamine, the natural racemate was resolved, and a series of 23 synthetic analogues was prepared, using as the end point the intracellular Ca2+ elevation in HEK-293 cells stably overexpressing either the human or the rat recombinant TRPV1. Key Results S-(+) evodiamine was more efficacious and potent than R-(−) evodiamine, and a new potent lead ( Evo30) was identified, more potent than the reference TRPV1 agonist, capsaicin. In general, potency and efficacy correlated with the lipophilicity of the analogues. Like other TRPV1 agonists, several synthetic analogues could efficiently desensitize TRPV1 to activation by capsaicin. Conclusions and Implications Evodiamine qualifies as structurally unique lead structure to develop new potent TRPV1 agonists/desensitizers. Linked Articles This article is part of a themed section on the pharmacology of TRP channels. To view the other articles in this section visit [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
26. Beyond Neuronal Heat Sensing: Diversity of TRPV1 Heat-Capsaicin Receptor-Channel Functions
- Author
-
Yaroslav M. Shuba
- Subjects
0301 basic medicine ,Cellular differentiation ,sensory neuron ,epithelia cells ,adipocytes ,TRPV1 ,Review ,Vanilloids ,Calcium in biology ,lcsh:RC321-571 ,smooth muscle ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Transient receptor potential channel ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Chemistry ,Sensory neuron ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Capsaicin ,Second messenger system ,lipids (amino acids, peptides, and proteins) ,030217 neurology & neurosurgery ,Neuroscience - Abstract
Transient receptor potential vanilloid 1 (TRPV1) is a calcium-permeable ion channel best known for its ability to be gated by the pungent constituent of red chili pepper, capsaicin, and related chemicals from the group of vanilloids as well as by noxious heat. As such, it is mostly expressed in sensory neurons to act as a detector of painful stimuli produced by pungent chemicals and high temperatures. Its activation is also sensitized by the numerous endogenous inflammatory mediators and second messengers, making it an important determinant of nociceptive signaling. Except for such signaling, though, neuronal TRPV1 activation may influence various organ functions by promoting the release of bioactive neuropeptides from sensory fiber innervation organs. However, TRPV1 is also found outside the sensory nervous system in which its activation and function is not that straightforward. Thus, TRPV1 expression is detected in skeletal muscle; in some types of smooth muscle; in epithelial and immune cells; and in adipocytes, where it can be activated by the combination of dietary vanilloids, endovanilloids, and pro-inflammatory factors while the intracellular calcium signaling that this initiates can regulate processes as diverse as muscle constriction, cell differentiation, and carcinogenesis. The purpose of the present review is to provide a clear-cut distinction between neurogenic TRPV1 effects in various tissues consequent to its activation in sensory nerve endings and non-neurogenic TRPV1 effects due to its expression in cell types other than sensory neurons.
- Published
- 2020
27. Vanilloids Hamper Caenorhabditis elegans Response to Noxious Heat
- Author
-
Jennifer Ben Salem, Francis Beaudry, and Bruno Nkambeu
- Subjects
Eugenol ,Zingerone ,chemistry.chemical_compound ,Transient receptor potential channel ,chemistry ,biology ,Capsaicin ,TRPV1 ,Biophysics ,biology.organism_classification ,TRPV ,Vanilloids ,Caenorhabditis elegans - Abstract
Eugenol, a known vanilloid, was frequently used in dentistry as a local analgesic in addition, antibacterial and neuroprotective effects were also reported. Eugenol, capsaicin and many vanilloids are interacting with the transient receptor potential vanilloid 1 (TRPV1) in mammals and are activated by noxious heat. The pharmacological manipulation of the TRPV1 has been shown to have therapeutic value. Caenorhabditis elegans (C. elegans) express TRPV orthologs (e.g. OCR-2, OSM-9) and it is a commonly used animal model system to study nociception as it displays a well-defined and reproducible nocifensive behavior. After exposure to vanilloid solutions, C. elegans wild type (N2) and mutants were placed on petri dishes divided in quadrants for heat stimulation. Thermal avoidance index was used to phenotype each tested C. elegans experimental groups. The results showed that eugenol, vanillin and zingerone can hamper nocifensive response of C. elegans to noxious heat (32°C – 35°C) following a sustained exposition. Also, the effect was reversed 6h post exposition. Furthermore, eugenol and vanillin did not target specifically the OCR-2 or OSM-9 but zingerone did specifically target the OCR-2 similarly to capsaicin. Further structural and physicochemical analyses were performed. Key parameters for quantitative structure-property relationships (QSPR), quantitative structure-activity relationships (QSAR) and frontier orbital analyses suggest similarities and dissimilarities amongst the tested vanilloids and capsaicin in accordance with the relative anti-nociceptive effects observed.
- Published
- 2020
28. Agonist and antagonist diverted twisting motions of single TRPV1 channel
- Author
-
Shoko Fujimura, Kowit Hengphasatporn, Muneyo Mio, Keigo Ikezaki, Kazuhiro Mio, Masahiro Kuramochi, Yasuteru Shigeta, Tai Kubo, Hiroshi Sekiguchi, and Yuji C. Sasaki
- Subjects
Agonist ,Physics ,medicine.drug_class ,TRPV1 ,Wild type ,Vanilloids ,Microsecond ,Transient receptor potential channel ,chemistry.chemical_compound ,chemistry ,Competitive antagonist ,Intramolecular force ,medicine ,Biophysics ,lipids (amino acids, peptides, and proteins) - Abstract
Transient receptor potential vanilloid type 1 (TRPV1) channels are activated by heat, vanilloids, and extracellular protons. Cryo-EM has revealed various conformations of TRPV1, and these structures suggest an intramolecular twisting motion in response to ligand binding. However, limited experimental data support this observation. Here we analyzed the intramolecular motion of TRPV1 using diffracted X-ray tracking (DXT). DXT analyzes trajectories of Laue spots generated from attached gold nanocrystals, and provides picometer spatial and microsecond time scale information about intramolecular motion. We observed that both an agonist and a competitive antagonist evoked rotating bias in TRPV1, though these biases were in opposing directions. Furthermore, the rotational bias generated by capsaicin was reversed between the wild type and the capsaicin-insensitive Y511A mutant. Our findings bolster the understanding of the mechanisms used activation and modulation of TRP channels, and this knowledge can be exploited for pharmacological usage such as inhibitor design.
- Published
- 2020
29. Endogenous and Exogenous Vanilloids Evoke Disparate TRPV1 Activation to Produce Distinct Neuronal Responses
- Author
-
Avi Priel, Rakesh Kumar, Matan Geron, and Adina Hazan
- Subjects
0301 basic medicine ,TRPV1 ,exovanilloids ,capsaicin ,Gq- GPCR ,Vanilloids ,03 medical and health sciences ,Transient receptor potential channel ,chemistry.chemical_compound ,0302 clinical medicine ,Noxious stimulus ,Pharmacology (medical) ,endovanilloids ,inflammatory pain ,Pharmacology ,musculoskeletal, neural, and ocular physiology ,lcsh:RM1-950 ,Depolarization ,Brief Research Report ,nociceptors ,030104 developmental biology ,Nociception ,lcsh:Therapeutics. Pharmacology ,chemistry ,nervous system ,Capsaicin ,030220 oncology & carcinogenesis ,Nociceptor ,lipids (amino acids, peptides, and proteins) ,bradykinin ,Neuroscience - Abstract
Neuronal signals are processed along the nociceptive pathway to convey discriminative information, which would manifest in the produced pain sensation. The transient receptor potential vanilloid 1 (TRPV1), an important signaling complex in nociceptors termini, is activated by different noxious stimuli that underlie distinct pain sensations. For example, while endovanilloids are associated with inflammatory pain and hypersensitivity through TRPV1 activation, the exovanilloid toxin, capsaicin, evokes an acute pain by activating this channel. Differences in the TRPV1 activation profile evoked by exogenous and endogenous vanilloids were suggested to underlie this disparity in pain sensations. However, the cellular processes that lead to these differences in pain sensation mediated by the same channel are not fully understood. Here, we sought to describe the neuronal response of TRPV1-expressing nociceptors to exo-and endovanilloids. To this end, we performed current-clamp recordings in rat trigeminal neurons exposed to either capsaicin or intracellular endovanilloids produced downstream of the bradykinin receptor BK2. Our results show that lipoxygenase metabolites generate persistent TRPV1-dependent action potential firing while capsaicin evokes robust depolarization and high-frequency firing that is quickly terminated by depolarization block. Additionally, we found that a weak TRPV1 activation prolongs action potential firing. Overall, our results indicate different firing patterns evoked by inflammatory mediators and capsaicin via TRPV1 that correlate with the respective subsequent pain sensation. These findings also suggest that differences in neuronal activation stem from the variable degree of TRPV1 activation they produce.
- Published
- 2020
30. Modulation of TRPV1 channel function by natural products in the treatment of pain
- Author
-
Manal A. Abbas
- Subjects
0301 basic medicine ,Modern medicine ,Fever ,TRPV1 ,Cell Culture Techniques ,Pain ,TRPV Cation Channels ,Pharmacology ,Toxicology ,Vanilloids ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Calcium imaging ,In vivo ,Animals ,Humans ,Analgesics ,Biological Products ,General Medicine ,030104 developmental biology ,chemistry ,Capsaicin ,030220 oncology & carcinogenesis ,lipids (amino acids, peptides, and proteins) ,Calcium ,Natural Product Research ,Function (biology) - Abstract
The capsaicin (vanilloid) receptor, TRPV1, is a heat-activated cation channel modulated by inflammatory mediators and contributes to acute and chronic pain. TRPV1 channel is one of the most researched and targeted mechanisms for the development of novel analgesics. Over the years, natural products have contributed enormously to the development of important therapeutic drugs used currently in modern medicine. A literature review was conducted using Medline, Google Scholar, and PubMed. Searching the literature resulted in listing 136 natural compounds that interacted with TRPV1 channel. These compounds were phytochemicals that belong to different chemical groups including vanilloids, flavonoids, alkaloids, terpenoids, terpenyl phenols, fatty acids, cannabinoids, sulfur_containing compounds, etc. Other natural TRPV1 modulators were of animal, fungal or bacterial origin. Some natural products were small agonists or antagonists of TRPV1. Others were protein venoms. Most in vitro studies utilized electrophysiological or calcium imaging techniques to study calcium flow through the channel using primary cultures of rat dorsal root and trigeminal ganglia. Other studies used hTRPV1 or rTRPV1 expressed in HEK239, CHO cells or Xenopus oocytes. In vivo studies concentrated on different pain models conducted mainly in mice and rats. In conclusion, natural products are highly diverse in their modulatory action on TRPV1. Many gaps in natural product research are present in distinguishing modality-specific from polymodal antagonists. Species' differences in TRPV1 functionality must be taken into account in any future study. Proceeding into clinical trials needs more efforts to discover potent TRPV1 antagonists devoid of hyperthermia, the main side effect.
- Published
- 2020
31. Moringin, A Stable Isothiocyanate from Moringa oleifera, Activates the Somatosensory and Pain Receptor TRPA1 Channel In Vitro
- Author
-
Angela Bassoli, Alessandro Leone, Aniello Schiano Moriello, Alberto Battezzati, Luciano De Petrocellis, Stefania Mazzini, Gigliola Borgonovo, and Simona Bertoli
- Subjects
Agonist ,isothiocyanates ,medicine.drug_class ,TRPM Cation Channels ,Pharmaceutical Science ,TRPA1 ion channel ,Pharmacology ,Transfection ,Article ,Vanilloids ,Nociceptive Pain ,Analytical Chemistry ,lcsh:QD241-441 ,Moringa ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,lcsh:Organic chemistry ,immune system diseases ,hemic and lymphatic diseases ,Drug Discovery ,TRPM8 ,medicine ,Humans ,Physical and Theoretical Chemistry ,Receptor ,TRPA1 Cation Channel ,030304 developmental biology ,Moringa oleifera ,0303 health sciences ,Plant Extracts ,Organic Chemistry ,Nociceptors ,food and beverages ,moringin ,Somatosensory Cortex ,bacterial infections and mycoses ,HEK293 Cells ,Nociception ,chemistry ,Chemistry (miscellaneous) ,Isothiocyanate ,Nociceptor ,Molecular Medicine ,lipids (amino acids, peptides, and proteins) ,030217 neurology & neurosurgery - Abstract
Moringa oleifera Lam. is a tropical plant widely used in traditional medicines and as a food supplement. It is characterized by the presence of glucosinolates and isothiocyanates, the stable isothiocyanate 4-[(&alpha, l-rhamnosyloxy)benzyl]isothiocyanate (moringin) has been widely studied for its bioactivity as hypoglycemic, antimicrobial, anticancer and in particular for its involvement in nociception and neurogenic pain. Moringa extracts and pure moringin were submitted to in vitro assays with the somatosensory TRPA1 ion channel, proving that moringin is a potent and effective agonist of this receptor involved in nociceptive function and pain states. Moringin do not activate or activates very weakly the vanilloids somatosensory channels TRPV1,2,3 and 4, and the melastatin cooling receptor TRPM8. The comparison of moringin&rsquo, s activity with other known agonists of natural origin is also discussed.
- Published
- 2020
- Full Text
- View/download PDF
32. Vanilloid-Like Agents: Potential Therapeutic Targeting of Platelets?
- Author
-
Adams, Murray J., Almaghrabi, Safa Y., Ahuja, Kiran D. K., and Geraghty, Dominic P.
- Subjects
- *
BLOOD platelet activation , *BLOOD platelet aggregation , *TRPV cation channels , *TRP channels , *CARDIOVASCULAR diseases - Abstract
The article presents an analysis of the mechanisms of involved in platelet aggregation and activation, focusinf on the properties of vanilloids and the receptor, TRPV1. It explores the effects of vanilloids, particularly capsaicinoids, on platelets to determine their potential therapeutic benefits. It suggests that vanilloids appear to modulate the function of platelets.
- Published
- 2013
- Full Text
- View/download PDF
33. Developmental and behavioral effects in neonatal and adult mice following prenatal activation of endocannabinoid receptors by capsaicin
- Author
-
Georgianna G. Gould, Norman Schanz, Sonya M. Bierbower, Lauren Tyrell, Alex Perchuk, Neal Joshi, Emmanuel S. Onaivi, Zoila Mora, and Ana Canseco-Alba
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Cannabinoid receptor ,Morpholines ,TRPV1 ,Embryonic Development ,TRPV Cation Channels ,Naphthalenes ,Article ,Vanilloids ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Rimonabant ,Pregnancy ,Internal medicine ,medicine ,Animals ,Pharmacology (medical) ,Maze Learning ,Receptors, Cannabinoid ,Cannabinoid Receptor Agonists ,Pharmacology ,Mice, Inbred BALB C ,Behavior, Animal ,business.industry ,Receptor Cross-Talk ,General Medicine ,Endocannabinoid system ,Conditioned place preference ,Benzoxazines ,030104 developmental biology ,Endocrinology ,chemistry ,Capsaicin ,Prenatal Exposure Delayed Effects ,030220 oncology & carcinogenesis ,Female ,lipids (amino acids, peptides, and proteins) ,business ,Capsazepine ,Injections, Intraperitoneal ,medicine.drug - Abstract
Despite the apparent abundance of ligand-gated transient receptor potential vanilloid type 1 (TRPV1) and possible cross talk between the endocannabinoid and endovanilloid systems in the central nervous system (CNS), it is unclear what role TRPV1 receptor activation in CNS plays in neurobehavioral development. We previously reported that capsaicin or WIN55212-2 induces risk aversion in the plus-maze test, which was dependent on the gender and mouse strain used. In this study, pregnant BALBc mice were administered capsaicin (1.0 or 4.0 mg/kg, i.p.) during the second week of gestation. Developmental effects of prenatal exposure to capsaicin were assessed in neonates, and behavioral effects were assessed in adult offspring. Gender- and dose-specific variations in ultrasonic vocalizations, weight gain, righting reflex, and general activity of the pups were observed. Prenatal exposure to capsaicin altered plus-maze performance, especially with further exogenous capsaicin challenge. Furthermore, dose- and gender-specific effects were evident in the conditioned place preference/aversion paradigm following conditioning with capsaicin in adult animals. The capsaicin-induced aversion in the plus-maze test was enhanced by WIN55212-2 and blocked by pretreatment with vanilloid antagonist capsazepine or the CB(1) receptor antagonist rimonabant, demonstrating an interaction between the endocannabinoid and endovanilloid systems in CNS. Taken together, the interaction between the endocannabinoid and endovanilloid signaling systems can be exploited for therapeutic applications in health and disease.
- Published
- 2018
34. Lipid-dependent sequential allosteric activation of heat-sensing TRPV1 channels by anchor-stereoselective 'hot' vanilloid compounds and analogs
- Author
-
Guangyu Wang
- Subjects
Sequential cooperativity ,QH301-705.5 ,Lipid-ligand interaction ,Allosteric regulation ,Biophysics ,Resiniferatoxin ,TRPV1 ,Cooperativity ,QD415-436 ,Review Article ,Active site stereoselectivity ,Biochemistry ,Vanilloids ,chemistry.chemical_compound ,Recessive transient ligand binding ,Phosphatidylinositol ,Biology (General) ,Ion channel ,musculoskeletal, neural, and ocular physiology ,Hydrogen bonding network ,Dominant steady-state ligand binding ,nervous system ,chemistry ,Capsaicin ,lipids (amino acids, peptides, and proteins) - Abstract
Both a silent resident phosphatidylinositol lipid and a “hot” vanilloid agonist capsaicin or resiniferatoxin have been shown to share the same inter-subunit binding pocket between a voltage sensor like domain and a pore domain in TRPV1. However, how the vanilloid competes off the resident lipid for allosteric TRPV1 activation is unknown. Here, the in sillico research suggested that anchor-stereoselective sequential cooperativity between an initial recessive transient silent weak ligand binding site and a subsequent dominant steady-state strong ligand binding site in the vanilloid pocket may facilitate the lipid release for allosteric activation of TRPV1 by vanilloids or analogs upon non-covalent interactions. Thus, the resident lipid may play a critical role in allosteric activation of TRPV1 by vanilloid compounds and analogs., Highlights • Four active vanilloid binding pockets as revealed by the cryo-EM structure of TRPV1 have no cooperativity between subunits. • Allosteric activation of TRPV1 by vanilloid compounds and analogs is lipid-dependent and anchor-stereoselective. • The resident and occluded lipid must be competed off for allosteric activation of TRPV1 by vanilloid compounds and analogs. • The first ligand binding is needed to release the resident lipid for the second ligand binding in the vanilloid pocket. • A lipid-free anchor facilitates the vanilloid ligand binding to remove the resident lipid from the active site in TRPV1. • Site accessibility controls sequential cooperative interactions of TRPV1 with vanilloids or analogs to open the channel. • The anchor stereoselectivity depends on the formation of a vanilloid bridge between two separated residues at the active site. • Different anchor stereoselectivities produce diverse recessive transient reaction intermediates or steps for TRPV1 opening. • Membrane hyperpolarization and depolarization may stabilize and loosen the resident lipid, for TRPV1 gating, respectively. • Phospholipids at N- and C- terminal domains may affect the cooperativity or the potency of the vanilloid ligands.
- Published
- 2021
35. Differential cytotoxicity and intracellular calcium-signalling following activation of the calcium-permeable ion channels TRPV1 and TRPA1
- Author
-
Shaya Lev, Andreas Leffler, Yaki Caspi, Mirjam Eberhardt, Alexander M. Binshtok, and Thomas Stueber
- Subjects
0301 basic medicine ,Physiology ,TRPV1 ,TRPV Cation Channels ,chemistry.chemical_element ,Calcium ,Endoplasmic Reticulum ,Calcium in biology ,Vanilloids ,03 medical and health sciences ,Transient receptor potential channel ,chemistry.chemical_compound ,Ganglia, Spinal ,Animals ,Humans ,Calcium Signaling ,TRPA1 Cation Channel ,Molecular Biology ,Cell Death ,Chemistry ,HEK 293 cells ,food and beverages ,Cell Biology ,Recombinant Proteins ,Mitochondria ,Cell biology ,Mice, Inbred C57BL ,HEK293 Cells ,030104 developmental biology ,nervous system ,lipids (amino acids, peptides, and proteins) ,Capsazepine ,Ion Channel Gating ,psychological phenomena and processes ,Intracellular - Abstract
Several members of the transient receptor channel (TRP) family can mediate a calcium-dependent cytotoxicity. In sensory neurons, vanilloids like capsaicin induce neurotoxicity by activating TRPV1. The closely related ion channel TRPA1 is also activated by irritants, but it is unclear if and how TRPA1 mediates cell death. In the present study we explored cytotoxicity and intracellular calcium signalling resulting from activation of TRPV1 and TRPA1, either heterologously expressed in HEK 293 cells or in native mouse dorsal root ganglion (DRG) neurons. While activation of TRPV1 by the vanilloids capsaicin, resiniferatoxin and anandamide results in calcium-dependent cell death, activation by protons and the oxidant chloramine-T failed to reduce cell viability. The TRPA1-agonists acrolein, carvacrol and capsazepine all induced cytotoxicity, but this effect is independent of TRPA1. Activation of both TRPA1 and TRPV1 triggers a strong influx of external calcium, but also a strong calcium-release from intracellular stores most likely including the endoplasmic reticulum (ER). Activation of TRPV1, but not TRPA1 also results in a strong increase of mitochondrial calcium both in HEK 293 cells and mouse DRG neurons. Our data demonstrate that activation of TRPV1, but not TRPA1 mediates a calcium-dependent cell death. While both receptors mediate a release of calcium from intracellular stores, only activation of TRPV1 seems to mediate a robust and probably lethal increase in mitochondrial calcium.
- Published
- 2017
36. Vanilloids
- Author
-
Gebhart, Gerald F., editor and Schmidt, Robert F., editor
- Published
- 2013
- Full Text
- View/download PDF
37. [6]-Dehydroshogaol, a minor component in ginger rhizome, exhibits quinone reductase inducing and anti-inflammatory activities that rival those of curcumin
- Author
-
Imm, Jeeyoung, Zhang, Goudong, Chan, Lok-Yan, Nitteranon, Viriya, and Parkin, Kirk L.
- Subjects
- *
GINGER , *FOOD composition , *QUINONE , *ENZYMES , *ANTI-inflammatory agents , *TURMERIC , *HEPATOCELLULAR carcinoma , *BLOOD cells - Abstract
Abstract: Quinone reductase (QR) inducing activity, a biomarker for Phase II enzyme induction, was detected in a crude ginger rhizome ethanolic extract using a murine hepatoma cell (Hepa 1c1c7) bioassay. An ethyl acetate-partitioned fraction became enriched in QR inducing activity with a CD value (concentration required to double QR specific activity) of 7μg/ml and was further separated by silica flash chromatography. The four major fractions recovered exhibited CD values ranging 10–20μg/mL for QR inducing activity. 1H NMR analysis revealed an abundance of gingerols in the first 3 fractions, and this led to a comparative assessment of QR inducing and anti-inflammatory activities among [6]-gingerol and structurally related vanilloids from ginger and other spices. [6]-Dehydroshogaol (DHSG), a minor component of fresh ginger, had QR inducing activity (CD=8.4μM) of comparable potency to the well known cancer preventive agent, curcumin (CD=4.3μM). In contrast, [6]-gingerol the major pungent component of ginger showed less potent QR inducing activity (CD=55μM) and capsaicin exhibited the weakest inducing activity (CD=103μM). [6]-Shogaol, [6]-DHSG and curcumin were also potent inhibitors of nitric oxide (NO) synthesis, inhibiting 50% NO evolution in activated macrophages at levels of 10–12μM (IC50 values). Comparatively, IC50 values for [6]-gingerol and capsaicin were about an order of magnitude greater (less potent) at 90μM and 169μM, respectively. This appears to be the first report of biological activities of [6]-DHSG, and Phase II enzyme-inducing ability of shogoal and gingerol. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
38. Activation of recombinant human TRPV1 receptors expressed in SH-SY5Y human neuroblastoma cells increases [Ca2+]i, initiates neurotransmitter release and promotes delayed cell death.
- Author
-
Lam, Patricia M. W., Hainsworth, Atticus H., Smith, Graham D., Owen, Davina E., Davies, James, and Lambert, David G.
- Subjects
- *
NEUROBLASTOMA , *NEUROTRANSMITTERS , *CATECHOLAMINES , *NORADRENALINE , *MEMBRANE proteins , *MONOMOLECULAR films - Abstract
The transient receptor potential (TRP) vanilloid receptor subtype 1 (TRPV1) is a ligand-gated, Ca2+-permeable ion channel in the TRP superfamily of channels. We report the establishment of the first neuronal model expressing recombinant human TRPV1 (SH-SY5YhTRPV1). SH-SY5Y human neuroblastoma cells were stably transfected with hTRPV1 using the Amaxa Biosystem (hTRPV1 in pIREShyg2 with hygromycin selection). Capsaicin, olvanil, resiniferatoxin and the endocannabinoid anandamide increased [Ca2+]i with potency (EC50) values of 2.9 nmol/L, 34.7 nmol/L, 0.9 nmol/L and 4.6 μmol/L, respectively. The putative endovanilloid N-arachidonoyl-dopamine increased [Ca2+]i but this response did not reach a maximum. Capsaicin, anandamide, resiniferatoxin and olvanil mediated increases in [Ca2+]i were inhibited by the TRPV1 antagonists capsazepine and iodo-resiniferatoxin with potencies ( KB) of ∼70 nmol/L and 2 nmol/L, respectively. Capsaicin stimulated the release of pre-labelled [3H]noradrenaline from monolayers of SH-SY5YhTRPV1 cells with an EC50 of 0.6 nmol/L indicating amplification between [Ca2+]i and release. In a perfusion system, we simultaneously measured [3H]noradrenaline release and [Ca2+]i and observed that increased [Ca2+]i preceded transmitter release. Capsaicin treatment also produced a cytotoxic response (EC50 155 nmol/L) that was antagonist-sensitive and mirrored the [Ca2+]I response. This model displays pharmacology consistent with TRPV1 heterologously expressed in standard non-neuronal cells and native neuronal cultures. The advantage of SH-SY5YhTRPV1 is the ability of hTRPV1 to couple to neuronal biochemical machinery and produce large quantities of cells. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
39. Structure–activity relationships of the ultrapotent vanilloid resiniferatoxin (RTX): The homovanillyl moiety
- Author
-
Appendino, Giovanni, Ech-Chahad, Abdellah, Minassi, Alberto, Bacchiega, Sara, Petrocellis, Luciano De, and Marzo, Vincenzo Di
- Subjects
- *
ACYL halides , *CELLS , *CHEMICAL elements , *CAPSAICIN - Abstract
Abstract: Starting from ROPA (2), analogues of RTX (1a) modified on the acyl side chain were prepared and evaluated for vanilloid activity in HEK-293 cells over-expressing the human recombinant TRPV1. The ROPA motif provided an enhancement of potency sufficient to expand the range of vanillyl surrogates to structural elements (e.g., an unsubstituted phenyl ring) that afford inactive analogues in compounds from the capsaicin series. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF
40. Neuromodulatory therapies in female pelvic medicine and reconstructive surgery: biological agents.
- Author
-
Schulte-Baukloh, Heinrich and Knispel, Helmut H.
- Subjects
- *
BOTULINUM toxin , *NEUROTOXIC agents , *PELVIC floor , *URINARY incontinence treatment , *URINATION disorders , *UROGYNECOLOGY , *THERAPEUTICS - Abstract
In recent years, important improvements in the management of patients with neurogenic or non-neurogenic detrusor overactivity and urge incontinence have been brought about by the introduction of vanilloids and botulinum toxins in urology. In this review we introduce the new therapeutic options, provides basic information, and summarize the results experienced so far. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
41. Developments in pharmacological therapy for the overactive bladder.
- Author
-
Chapple, Christopher R. and Gormley, E. Ann
- Subjects
- *
BLADDER disease treatment , *URINARY organ diseases , *MUSCARINIC receptors , *ADRENERGIC receptors , *ANTIDEPRESSANTS , *VASOPRESSIN , *PROSTAGLANDINS , *THERAPEUTICS - Abstract
The article provides a summary of developments in pharmacological therapy for the overactive bladder (OAB), particularly with regards to available antimuscarinic drugs and the newer non-anticholinergic drugs. Antimuscarinic drugs include tolterodine, trospium, darifenacin and solifenacin. Other types of drugs are those acting on membrane channels, those with mixed actions, adrenoceptors, antidepressants, prostaglandin synthesis inhibitors and vasopressin analogues.
- Published
- 2006
- Full Text
- View/download PDF
42. Induction of apoptosis in prostate tumor PC-3 cells and inhibition of xenograft prostate tumor growth by the vanilloid capsaicin.
- Author
-
Sánchez, A. M., Sánchez, M. G., Malagarie-Cazenave, S., Olea, N., and Díaz-Laviada, I.
- Subjects
PROSTATE tumors ,CANCER cells ,APOPTOSIS ,TUMOR growth ,CAPSAICIN - Abstract
Capsaicin, the pungent ingredient of hot chilli pepper, has been recently shown to induce apoptosis in several cell lines through a not well known mechanism. Here, we investigated the role of the vanilloid capsaicin in the death regulation of the human cancer androgen-resistant cell line PC-3. Capsaicin inhibited the growth of PC-3 with an IC
50 of 20 μM cells and induced cell apoptosis, as assessed by flow cytometry and nuclei staining with DAPI. Capsaicin induced apoptosis in prostate cells by a mechanism involving reactive oxygen species generation, dissipation of the mitochondrial inner transmembrane potential (ΔΨm ) and activation of caspase 3. Capsaicin-induced apoptosis was not reduced by the antagonist capsazepine in a dose range from 0.1 μM to 20 μM, suggesting a receptor-independent mechanism. To study the in vivo effects of capsaicinoids, PC-3 cells were grown as xenografts in nude mice. Subcutaneous injection of either capsaicin or capsazepine (5 mg/kg body weight) in nude mice suppressed PC-3 tumor growth in all tumors investigated and induced apoptosis of tumor cells. Our data show a role for capsaicin against androgen-independent prostate cancer cells in vitro and in vivo and suggest that capsaicin is a promising anti-tumor agent in hormone-refractory prostate cancer, which shows resistance to many chemotherapeutic agents. [ABSTRACT FROM AUTHOR]- Published
- 2006
- Full Text
- View/download PDF
43. Capsaicin stimulates the non-store-operated Ca2+ entry but inhibits the store-operated Ca2+ entry in neutrophils
- Author
-
Wang, Jih-Pyang, Tseng, Chia-Shun, Sun, Shu-Ping, Chen, Yu-San, Tsai, Chi-Ren, and Hsu, Mei-Feng
- Subjects
- *
CAPSAICIN , *MESSENGER RNA , *ORGANONITROGEN compounds , *CELL membranes - Abstract
Abstract: Rat neutrophils express the mRNA encoding for transient receptor potential (TRP) V1. However, capsaicin-stimulated [Ca2+]i elevation occurred only at high concentrations (≥100 μM). This response was substantially decreased in a Ca2+-free medium. Vanilloids displayed similar patterns of Ca2+ response with the rank order of potency as follows: scutigeral>resiniferatoxin>capsazepine>capsaicin=olvanil>isovelleral. Arachidonyl dopamine (AAD), an endogenous ligand for TRPV1, failed to desensitize the subsequent capsaicin challenge. Capsaicin-induced Ca2+ response was not affected by 8-bromo-cyclic ADP-ribose (8-Br-cADPR), the ryanodine receptor blocker, but was slightly attenuated by 1-[6-[17β-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U-73122), the inhibitor of phospholipase C-coupled processes, 1-[β-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole (SKF-96365), the blocker of receptor-gated and store-operated Ca2+ (SOC) channels, 2-aminoethyldiphenyl borate (2-APB), the blocker of D-myo-inositol 1,4,5-trisphospahte (IP3) receptor and Ca2+ influx, and by ruthenium red, a blocker of TRPV channels, and enhanced by the Ca2+ channels blocker, cis-N-(2-phenylcyclopentyl)azacyclotridec-1-en-2-amine (MDL-12330A) and Na+-deprivation. In addition, capsaicin had no effect on the plasma membrane Ca2+-ATPase activity or the production of nitric oxide (NO) and reactive oxygen intermediates (ROI) or on the total thiols content. Capsaicin (≥100 μM) inhibited the cyclopiazonic acid (CPA)-induced store-operated Ca2+ entry (SOCE). In the absence of external Ca2+, the robust Ca2+ entry after subsequent addition of Ca2+ was decreased by capsaicin in CPA-activated cells. Capsaicin alone increased the actin cytoskeleton, and also increased the actin filament content in cell activation with CPA. These results indicate that capsaicin activates a TRPV1-independent non-SOCE pathway in neutrophils. The reorganization of the actin cytoskeleton is probably involved in the capsaicin inhibition of SOCE. [Copyright &y& Elsevier]
- Published
- 2005
- Full Text
- View/download PDF
44. Expression of the transient receptor potential vanilloid 1 (TRPV1) in LNCaP and PC-3 prostate cancer cells and in human prostate tissue
- Author
-
Sánchez, María G., Sánchez, Ana M., Collado, Beatriz, Malagarie-Cazenave, Sophie, Olea, Nuria, Carmena, María J., Prieto, Juan C., and Díaz-Laviada, Inés
- Subjects
- *
PROSTATE , *DNA polymerases , *HYDROGEN-ion concentration , *FLUORESCENCE microscopy - Abstract
Abstract: Vanilloid receptor subtype-1 (TRPV1), the founding member of the vanilloid receptor-like transient receptor potential channel family, is a non-selective cation channel that responds to noxious stimuli such as low pH, painful heat and irritants. In the present study, we show, as means of reverse transcriptase-polymerase chain reaction and Western blot analysis, that the vanilloid TRPV1 receptor is expressed in the prostate epithelial cell lines PC-3 and LNCaP as well as in human prostate tissue. The kinetic parameters inferred from [125I]-resiniferatoxin binding were in concordance with data of TRPV1 receptors expressed in other tissues. The contribution of the endogenously expressed TRPV1 channel to intracellular calcium concentration increase in the prostate cells was studied by measuring changes in Fura-2 fluorescence by fluorescence microscopy. Addition of capsaicin, (R)-methanandamide and resiniferatoxin to prostate cells induced a dose-dependent increase in the intracellular calcium concentration that was reversed by the vanilloid TRPV1 receptor antagonist capsazepine. These results indicate that the vanilloid TRPV1 receptor is expressed and functionally active in human prostate cells. [Copyright &y& Elsevier]
- Published
- 2005
- Full Text
- View/download PDF
45. Vanilloids
- Author
-
Schmidt, Robert F., editor and Willis, William D., editor
- Published
- 2007
- Full Text
- View/download PDF
46. P2X3-Immunoreactive Nerve Fibres in Neurogenic Detrusor Overactivity and the Effect of Intravesical Resiniferatoxin
- Author
-
Brady, Ciaran M., Apostolidis, Apostolos, Yiangou, Yiangos, Baecker, Preston A., Ford, Anthony P., Freeman, Alex, Jacques, Thomas S., Fowler, Clare J., and Anand, Praveen
- Subjects
- *
PURINERGIC receptors , *SENSORY neurons , *BLADDER , *NERVE fibers , *NEURONS - Abstract
Objectives: The ATP-gated purinergic receptor P2X3 is expressed by small diameter sensory neurons and has been identified in normal and neurogenic human bladder suburothelial fibres. Animal models have shown that ATP is released by the urothelium during bladder distension, suggesting a mechanosensory role for P2X3 receptors in normal bladder function. Successful treatment of spinal neurogenic detrusor overactivity (NDO) with intravesical resiniferatoxin (RTX), which partly acts on suburothelial C fibres, provides evidence for the emergence of a C fibre-mediated spinal reflex. The aim of this study was to investigate the possible role of P2X3-positive innervation in this pathological voiding reflex by comparing suburothelial P2X3 immunoreactivity of controls and in patients with NDO before and after intravesical RTX.Methods: Bladder biopsies were obtained from 8 controls and 20 patients with refractory NDO enrolled in a trial of intravesical RTX. P2X3 nerve fibre density and intensity were studied in the specimens by immunohistochemistry.Results: P2X3-IR nerve fibres were significantly increased in patients with NDO compared to controls (
p=0.014 ). Thirteen patients had pre- and post-RTX biopsies available for immunohistochemistry; 5 of them responded clinically and 8 were non-responders. In the 5 patients who responded to RTX, there was a significant decrease in P2X3-positive fibres (p=0.032 ), whereas in non-responders, P2X3-IR nerve fibre density did not change significantly.Conclusions: In patients with NDO, the numbers of P2X3-IR nerve fibres were increased in the suburothelium. There was a significant decrease in P2X3 immunoreactivity in responders to RTX, indicating a potential pathophysiological role for the P2X3 expressing fibres. [Copyright &y& Elsevier]- Published
- 2004
- Full Text
- View/download PDF
47. Mechanisms of vanilloid-induced apoptosis.
- Author
-
Hail, Jr., Numsen
- Subjects
APOPTOSIS ,PHYTOCHEMICALS ,THERAPEUTICS ,GENETIC toxicology ,NEUROTOXICOLOGY - Abstract
Chemical compounds that contain the vanillyl moiety (4-hydroxy-3-methoxybenzyl) are collectively classified as vanilloids. Vanilloid phytochemicals can be found in a variety of sources, some of which are routinely consumed by humans throughout the world. The dietary and/or medicinal use of vanilloids may be effective in inhibiting or reversing carcinogenesis, which has sparked a considerable interest in these compounds as potential chemopreventive or chemotherapeutic agents. Certain vanilloids are also valuable as pharmacological tools for investigating neurobiology, and have been proven effective in alleviating neurogenic pain and inflammation. Recently several vanilloids have demonstrated the ability to induce apoptosis in various cell types. Vanilloids can interact with proteins and membranes to initiate pleiotropic effects, some of which are potentially cytotoxic. Certain vanilloids bind to cation channels on nociceptive sensory neurons to regulate Ca
2+ uptake, which can promote neurotoxicity resulting in apoptosis and necrosis. Furthermore, some vanilloids appear to interfere with enzymatic processes in the plasma membrane and the mitochondria by functioning as coenzyme Q antagonist. This can promote reactive oxygen species production and/or the disruption of redox homeostasis resulting in apoptosis. This review will examine the cellular targets, cytotoxic effects, and the downstream effector mechanisms associated with vanilloid-induced apoptosis. [ABSTRACT FROM AUTHOR]- Published
- 2003
- Full Text
- View/download PDF
48. Cannabinoid modulation of sensory neurotransmission via cannabinoid and vanilloid receptors: Roles in regulation of cardiovascular function
- Author
-
Ralevic, Vera, Kendall, David A., Randall, Michael D., and Smart, Darren
- Subjects
- *
CANNABINOIDS , *SENSORY neurons , *CARDIOVASCULAR system - Abstract
Capsaicin-sensitive sensory nerves are widely distributed in the cardiovascular system. They are activated by a variety of physical and chemical stimuli, characteristically by capsaicin acting via the vanilloid receptor VR1, and have a role in the regulation of peripheral vascular resistance and maintenance of homeostasis via their afferent and efferent functions. Cannabinoids, a recently discovered family of extracellular signalling molecules, can act at cannabinoid (CB) receptors expressed on sensory nerves, to cause inhibition of sensory neurotransmitter release. There is recent evidence, however, that anandamide, an endogenous cannabinoid, can activate VR1, coexpressed with CB receptors on the same sensory nerve terminals, causing a release of sensory neurotransmitter, vasorelaxation and hypotension. Hence, anandamide can elicit opposite actions, inhibition via CB receptors and excitation via VR1, on sensory neurotransmission. The possible biological significance of this is discussed. [Copyright &y& Elsevier]
- Published
- 2002
- Full Text
- View/download PDF
49. Sourcing the Code: Searching for the Evolutionary Origins of Cannabinoid Receptors, Vanilloid Receptors, and Anandamide.
- Author
-
McPartland, John M. and Pruitt, Patty
- Abstract
Two cannabinoid (CB) receptors are known in humans, CB1 and CB2. They are phylogenetically ancient. Studies suggest CB receptors occur in mammals, birds, amphibians, fish, sea urchins, mollusks, leeches, and Hydra vulgaris. The CB receptor genes from some of these animals have been cloned and sequenced. These sequences were used to construct a phylogenetic tree of CB genes. The gene tree is rooted in an ancestral CB gene that predates the divergence of vertebrates and invertebrates. Thus the primordial CB receptor evolved at least 600 million years ago, a date broadly consistent with the Cambrian explosion. Since then, one clade of invertebrates, the Ecdysozoa, has secondarily lost the genes coding CB receptors. There is no evidence that animals obtained CB genes from other organisms via horizontal gene transfer. We hypothesize that the primordial CB receptor diverged from a related G-protein coupled receptor, and it linked with a pre-existing ligand, anandamide. Anandamide serves as a ligand for CB receptors as well as vanilloid (VR) receptors. VR receptors regulate the sensation of pain, and may also modulate mood and memory. Our phylogenetic analysis suggests that VR receptors evolved before CB receptors, so anandamide first served as a VR ligand. We speculate that CB receptors, lacking selective constraints, subsequently acquired a mutation that coupled them with 2-AG. A better understanding of CB and VR receptors man enable us to combine their beneficial effects. Dual-signaling ligands such as anandamide have excellent therapeutic potential as analgesics, vasodilators, and anti-cancer agents. [ABSTRACT FROM PUBLISHER]
- Published
- 2002
- Full Text
- View/download PDF
50. High-Content Screening Identifies Vanilloids as a Novel Class of Inhibitors of NET Formation
- Author
-
Emanuela Pesce, Roberta Bertelli, Gian Marco Ghiggeri, Elvira Sondo, and Nicoletta Pedemonte
- Subjects
lcsh:Immunologic diseases. Allergy ,0301 basic medicine ,Programmed cell death ,Neutrophils ,Cell ,Immunology ,Drug Evaluation, Preclinical ,high-content screening ,Extracellular Traps ,Vanilloids ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,inhibitors ,Hydroxybenzoates ,medicine ,Humans ,Immunology and Allergy ,Original Research ,Chemistry ,NETosis ,neutrophil ,NETs ,Biological activity ,Neutrophil extracellular traps ,Cell biology ,Cytosol ,030104 developmental biology ,medicine.anatomical_structure ,Lytic cycle ,High-content screening ,lcsh:RC581-607 ,vanilloids ,030215 immunology - Abstract
Neutrophils migrate to sites of infection where they phagocytose, degranulate, and/or, in the presence of appropriate stimuli, release decondensed chromatin strands (called neutrophil extracellular traps, NETs) for trapping and possibly killing microorganisms. NET formation is characterized by marked morphological cell changes, in particular within the nucleus. Lytic NET formation can be observed in neutrophils undergoing cell death, which is referred to as NETosis. Dysregulation of NET production and/or degradation can exert pathogenic effects, contributing to the pathogenesis of various diseases, including cystic fibrosis, autoimmune diseases and inflammatory conditions. By employing a phenotypic assay based on high-content imaging and analysis, we screened a library of biologically active compounds and identified vanilloids as a novel class of chemical compounds able to hinder NETosis induction and NET release. Vanilloids also markedly decrease cytosolic ROS production. The identification of novel vanilloid NET inhibitors, able to stop excessive or aberrant NET production might offer new therapeutic options for those disorders displaying NET overproduction.
- Published
- 2019
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.