36 results on '"Shiraishi, Mitsuya"'
Search Results
2. Vasomotor effects of noradrenaline, 5-hydroxytryptamine, angiotensin II, bradykinin, histamine, and acetylcholine on the bat (Rhinolophus ferrumequinum) basilar artery
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Islam, Md. Zahorul, Kojima, Shusuke, Sameshima, Masamichi, Obi, Takeshi, Yamazaki-Himeno, Emi, Shiraishi, Mitsuya, and Miyamoto, Atsushi
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- 2021
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3. α-MSH-induced activation of spinal MC1R but not MC4R enhances colorectal motility in anaesthetised rats
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Ueda, Hiromi H., Naitou, Kiyotada, Nakamori, Hiroyuki, Horii, Kazuhiro, Shiina, Takahiko, Masatani, Tatsunori, Shiraishi, Mitsuya, and Shimizu, Yasutake
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- 2021
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4. Habu snakes (Protobothrops flavoviridis) show variation in thoracic aortic vasoreactivity between adjacent Japanese islands.
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OOTAWA, Tomoki, WU, Siyuan, SEKIO, Ryoya, SMITH, Henry, ISLAM, Md Zahorul, NGUYEN, Ha Thi Thanh, UNO, Yasuhiro, SHIRAISHI, Mitsuya, and MIYAMOTO, Atsushi
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SNAKES ,PIT vipers ,ANIMAL populations ,AORTA ,ANIMAL variation - Abstract
Habu snakes (Protobothrops flavoviridis) are pit vipers found in the geographically adjacent but ecologically divergent islands of Tokunoshima and Amami-Oshima in southwestern Japan. Abiotic factors can cause variation in animal populations between the two islands, and Habu snakes may show such intraspecific physiological variation. We therefore evaluated the vasoreactivity in aortas isolated from the Habu of both islands. Tokunoshima Habu showed significantly greater contractile responses to angiotensin (Ang) II, acetylcholine (ACh) and noradrenaline, and significantly higher affinities (pEC50) for Ang II and ACh, than Amami-Oshima Habu. ACh caused contractions in aortas from both populations, a finding previously unreported in snakes. Our findings indicate that vasoreactivity may differ between Tokunoshima and Amami-Oshima Habu. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Hypertension alters the endothelial-dependent biphasic response of bradykinin in isolated Microminipig basilar artery
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Zahorul Islam, Md., Kawaguchi, Hiroaki, Miura, Naoki, Miyoshi, Noriaki, Yamazaki-Himeno, Emi, Shiraishi, Mitsuya, Miyamoto, Atsushi, and Tanimoto, Akihide
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- 2017
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6. Characterization of Vasoreactivity in a Semi-Arboreal Snake, the Tokara Habu (Protobothrops tokarensis).
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Ootawa, Tomoki, Wu, Siyuan, Sekio, Ryoya, Smith, Henry, Islam, Md. Zahorul, Nguyen, Ha Thi Thanh, Uno, Yasuhiro, Shiraishi, Mitsuya, and Miyamoto, Atsushi
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SNAKE venom ,SNAKES ,REPTILES ,THORACIC aorta ,ANGIOTENSIN II ,ADRENERGIC receptors ,BRADYKININ ,NORADRENALINE - Abstract
Simple Summary: Snakes are reptiles that have evolved over a period of approximately 170 million years, adapting to life in different habitats, including water (rivers and oceans), on the ground, in trees, and underground. The distance from the heart to the brain is known to be shorter in arboreal snakes compared to terrestrial ones, indicating that differences in habitat may also affect vascular response. In this study, we attempted to characterize vasoreactivity in the Tokara habu, a semi-arboreal snake. The Tokara habu snakes demonstrated a number of relaxation responses to various vasoactive substances, and they showed complex vasoreactivity, a contrast to the simple vasoreactivity seen in terrestrial snakes. These results suggest that the Tokara habu's distinctive, complex vasoreactivity may reflect adaptation to its semi-arboreal environment. Comparisons of vascular responses may be useful as a new approach to behavioral and ecological studies for species that are difficult to observe in the field. Vasoreactivity is relatively well documented in terrestrial snakes but has previously been investigated in only one semi-arboreal snake species. Consequently, the extent to which vasoreactivity is common across snake taxa or varies by habitat is unclear. The Tokara habu (Protobothrops tokarensis) is a semi-arboreal snake endemic to only two small adjacent Japanese islands, and hence a useful species for further investigation of vasoreactivity. We evaluated responses to known vasoactive substances in thoracic aortas isolated from Tokara habu. Under resting tension, noradrenaline and angiotensin II induced concentration-dependent contraction, but acetylcholine, serotonin (5-hydroxytriptamine; 5-HT), and isoproterenol induced relaxation followed by contraction. Histamine and rattlesnake bradykinin had no effect. Experiments with receptor-specific antagonists suggest that M
1 and M3 receptors are involved in the acetylcholine-induced response; 5-HT1 , 5-HT2 , and 5-HT7 receptors in the serotonin-induced response; and β1 and β2 adrenoceptors in isoproterenol-induced relaxation. This is the first report on such response patterns in snakes (including serotonin- and isoproterenol-induced relaxation). Nitric oxide may be involved in acetylcholine-induced relaxation but not in the responses to serotonin or isoproterenol. In contrast to the uniform vasoreactivity observed in terrestrial snakes, the vasoreactivity of semi-arboreal snakes may be governed by diverse regulatory mechanisms. [ABSTRACT FROM AUTHOR]- Published
- 2023
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7. Methylmercury affects cerebrovascular reactivity to angiotensin II and acetylcholine via Rho-kinase and nitric oxide pathways in mice
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Islam, Md. Zahorul, Van Dao, Cuong, Shiraishi, Mitsuya, and Miyamoto, Atsushi
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- 2016
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8. Enzymatic synthesis and RNA interference of nucleosides incorporating stable isotopes into a base moiety
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Hatano, Akihiko, Shiraishi, Mitsuya, Terado, Nanae, Tanabe, Atsuhiro, and Fukuda, Kenji
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- 2015
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9. Reduced Nitric Oxide Synthase Involvement in Aigamo Duck Basilar Arterial Relaxation.
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Wu, Siyuan, Ootawa, Tomoki, Sekio, Ryoya, Smith, Henry, Islam, Md. Zahorul, Nguyen, Ha Thi Thanh, Uno, Yasuhiro, Shiraishi, Mitsuya, and Miyamoto, Atsushi
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NITRIC-oxide synthases ,VASCULAR endothelium ,AVIAN influenza A virus ,BASILAR artery ,VASCULAR endothelial cells ,HISTAMINE receptors ,BRADYKININ receptors - Abstract
Simple Summary: The basilar artery is a vital cerebral blood vessel common in most vertebrates and constantly supplies blood to the hindbrain where many vital functions are coordinated. Avian basilar arterial responsiveness to vasoactive substances has been characterized only in chickens. In this artery, the endothelium plays an important role in relaxation, and endothelial dependence may explain the lethality of the highly pathogenic avian influenza virus, which reportedly induces apoptosis in the cerebrovascular endothelium. Our present results in ducks suggest a contrast to the previously reported results in chickens with regard to basilar arterial relaxation: The involvement of endothelial nitric oxide as a relaxing factor appears to be reduced in duck basilar arteries. Our research may help scientists to better understand the resistance to the highly pathogenic avian influenza virus that may be conferred by the cerebrovascular endothelium in ducks. The basilar arterial endothelium mediates blood vessel relaxation partly through the release of nitric oxide (NO). Apoptosis of cerebrovascular endothelial cells is linked to a high mortality rate in chickens infected with the highly pathogenic avian influenza virus, but interestingly, ducks exhibit a greater resistance to this virus. In this study, we examined the responsiveness of duck basilar arteries (BAs) to various vasoactive substances, including 5-hydroxytryptamine (5-HT), histamine (His), angiotensin (Ang) II, noradrenaline (NA), acetylcholine (ACh), and avian bradykinin ornithokinin (OK), aiming to characterize the receptor subtypes involved and the role of endothelial NO in vitro. Our findings suggest that arterial contraction is mediated with 5-HT
1 and H1 receptors, while relaxation is induced with β3 -adrenergic and M3 receptors. Additionally, OK elicited a biphasic response in duck BAs, and Ang II had no effect. Endothelial NO appears to be crucial in relaxation mediated with M3 and OK receptors but not β3 -adrenergic receptors in the duck BA. The reduced endothelial NO involvement in the receptor-mediated relaxation response in duck BAs represents a clear difference from the corresponding response reported in chicken BAs. This physiological difference may explain the differences in lethality between ducks and chickens when vascular endothelial cells are infected with the virus. [ABSTRACT FROM AUTHOR]- Published
- 2023
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10. Rho-kinase and the nitric oxide pathway modulate basilar arterial reactivity to acetylcholine and angiotensin II in streptozotocin-induced diabetic mice
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Islam, Md. Zahorul, Van Dao, Cuong, Miyamoto, Atsushi, and Shiraishi, Mitsuya
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- 2017
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11. Relationship between Regional Distribution of Centenarians and Drinking Water Hardness in the Amami Islands, Kagoshima Prefecture, Japan.
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Suzuki, Mai, Wu, Siyuan, Ootawa, Tomoki, Smith, Henry, Shiraishi, Mitsuya, Miyamoto, Atsushi, Matsuoka, Yuki, Sawa, Sawako, Mori, Mari, Mori, Hideki, and Yamori, Yukio
- Abstract
People who drink naturally hardened water may experience longevity-enhancing effects. In this study, we investigated water hardness and longevity from both geological and epidemiological perspectives in Japan's Amami islands, where drinking water is drawn from coralline or non-coralline bedrock. We investigated drinking water hardness, limestone bedrock occupancy, and the centenarian rate (number per 10,000 population) by municipality across four adjacent islands (Amami-Oshima (non-coralline), Tokunoshima, Okinoerabu, and Yoron (predominantly coralline)). Limestone was strongly correlated with water hardness (r = 0.99; p < 0.01), occupying more than 80% of the bedrock where the water was the hardest (Tokunoshima's Isen municipality: 86.5%; Yoron: 82.9%) and being scarcely detectable in Amami-Oshima (0.0 to 0.2%), where the water was the least hard. The centenarian rate was also strongly correlated with water hardness (r = 0.84, p < 0.01), with the highest figures in Yoron (29.7) and Isen (29.2), and the lowest in Amami-Oshima (0.0 to 12.2). Therefore, we hypothesize a potentially beneficial effect of hard water on longevity when that water is drawn from coralline limestone. Water hardness is determined by the water content of calcium and magnesium and may plausibly influence life expectancy through a preventative effect against cardiovascular disease. Our findings are of interest to current debates about future global access to drinking water and its quality. [ABSTRACT FROM AUTHOR]
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- 2023
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12. Cholesterol enrichment of rabbit platelets enhances the Ca2 + entry pathway induced by platelet-derived secondary feedback agonists
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Shiraishi, Mitsuya, Tamura, Kazuya, Egoshi, Mina, and Miyamoto, Atsushi
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- 2013
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13. A comprehensive analysis of six forms of cytochrome P450 2C (CYP2C) in pigs.
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Uno, Yasuhiro, Morikuni, Saho, Shiraishi, Mitsuya, Asano, Atsushi, Kawaguchi, Hiroaki, Murayama, Norie, and Yamazaki, Hiroshi
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CYTOCHROME P-450 ,SWINE ,DRUG metabolism ,SMALL intestine ,GENE clusters - Abstract
Pigs are an important species used in drug metabolism studies; however, the cytochromes P450 (P450s or CYPs) have not been fully investigated in pigs. In this study, pig CYP2C32, CYP2C33, CYP2C34, CYP2C36, CYP2C42, and CYP2C49 cDNAs were isolated and found to contain open reading frames of 490 or 494 amino acids that shared 64–82% sequence identity with human CYP2C8/9/18/19. Pig CYP2C genes formed a gene cluster in a genomic region that corresponded to that of the human CYP2C cluster; an additional gene cluster was formed by pig CYP2C33a and CYP2C33b distant from the first cluster but located in the same chromosome. Among the tissues analysed, these pig CYP2C mRNAs were preferentially expressed in liver, small intestine, and/or kidney; pig CYP2C49, CYP2C32, CYP2C34, and CYP2C33 mRNAs were the most abundant CYP2C mRNAs in liver, jejunum, ileum, and kidney, respectively. Metabolic assays showed that pig CYP2C proteins (heterologously expressed in Escherichia coli) metabolised typical human CYP2C substrates diclofenac, warfarin, and/or omeprazole. The results suggest that these pig CYP2Cs are functional enzymes able to metabolise human CYP2C substrates in liver and small intestine, just as human CYP2Cs do. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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14. A highly sensitive technique to measure myosin regulatory light chain phosphorylation: the first quantification in renal arterioles
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Takeya, Kosuke, Loutzenhiser, Kathy, Shiraishi, Mitsuya, Loutzenhiser, Rodger, and Walsh, Michael P.
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Myosin -- Physiological aspects ,Myosin -- Health aspects ,Myosin -- Research ,Phosphorylation -- Physiological aspects ,Phosphorylation -- Health aspects ,Phosphorylation -- Research ,Renal artery -- Physiological aspects ,Renal artery -- Health aspects ,Renal artery -- Research ,Biological sciences - Abstract
Phosphorylation of the 20-kDa myosin regulatory light chains ([LC.sub.20]) plays a key role in the regulation of smooth muscle contraction. The level of [LC.sub.20] phosphorylation is governed by the relative activities of myosin light chain kinase and phosphatase pathways. The regulation of these two pathways differs in different smooth muscle types and in the actions of different vasoactive stimuli. Little is known concerning the regulation of [LC.sub.20] phosphorylation in the renal microcirculation. The available pharmacological probes are often nonspecific, and current techniques to directly measure [LC.sub.20] phosphorylation are not sensitive enough for quantification in small arterioles. We describe here a novel approach to address this important issue. Using SDS-PAGE with polyacrylamide-bound [Mn.sup.2+]-phosphate-binding tag and enhanced Western blot analysis, we were able to detect [LC.sub.20] phosphorylation using as little as 5 pg (250 amol) of isolated [LC.sub.20]. Phosphorylated and unphosphorylated [LC.sub.20] were detected in single isolated afferent arterioles, and [LC.sub.20] phosphorylation levels could be accurately quantified in pooled samples of three arterioles ( afferent arteriole; Phos-tag SDS-PAGE
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- 2008
15. Inhibition of protein kinase C-mediated contraction by Rho kinase inhibitor fasudil in rabbit aorta
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Shimomura, Erika, Shiraishi, Mitsuya, Iwanaga, Takahiro, Seto, Minoru, Sasaki, Yasuharu, Ikeda, Masahiro, and Ito, Katsuaki
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- 2004
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16. Modulation of PG[F.sub.2[alpha]]-and hypoxia-induced contraction of rat intrapulmonary artery by p38 MAPK inhibition: a nitric oxide-dependent mechanism
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Knock, Greg A., De Silva, Anushika S., Snetkov, Vladimir A., Siow, Richard, Thomas, Gavin D., Shiraishi, Mitsuya, Walsh, Michael P., Ward, Jeremy P.T., and Aaronson, Philip I.
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Nitric oxide -- Chemical properties ,Nitric oxide -- Research ,Hypoxia -- Research ,Mitogens -- Research ,Protein kinases -- Research ,Biological sciences - Abstract
The mechanisms through which p38 mitogen-activated protein kinase (p38 MAPK) is involved in smooth muscle contraction remain largely unresolved. We examined the role of p38 MAPK in prostaglandin [F.sub.2[alpha]] (PG[F.sub.2[alpha]])-induced vasoconstriction and in hypoxic pulmonary vasoconstriction (HPV) of rat small intrapulmonary arteries (IPA). The p38 MAPK inhibitors SB-203580 and SB-202190 strongly inhibited PG[F.sub.2[alpha]]-induced vasoconstriction, with I[C.sub.50]s of 1.6 and 1.2 [micro]M, whereas the inactive analog SB-202474 was ~30-fold less potent. Both transient and sustained phases of HPV were suppressed by SB-203580, but not by SB-202474 (both 2 [micro]M). Western blot analysis revealed that PG[F.sub.2[alpha]] (20 [micro]M) increased phosphorylation of p38 MAPK and of heat shock protein 27 (HSP27), and this was abolished by SB-203580 but not by B-202474 (both 2 [micro]M). Endothelial denudation or blockade of endothelial nitric oxide (NO) synthase with [N.sup.[omega]]-nitro-L -arginine methyl ester (L-NAME) significantly suppressed the relaxation of PG[F.sub.2[alpha]]-constricted IPA by SB-203580, but not by SB-202474. Similarly, the inhibition of HPV by SB-203580 was prevented by prior treatment with L-NAME. SB-203580 (2 [micro]M), but not SB-202474, enhanced relaxation-induced by the NO donor S-nitroso-N-acetylpenicillamine (SNAP) in endothelium-denuded IPA constricted with PG[F.sub.2[alpha]]. In [alpha]-toxin-permeabilized IPA, SB-203580-induced relaxation occurred in the presence but not the absence of the NO donor sodium nitroprusside (SNP); SB-202474 was without effect even in the presence of SNP. In intact IPA, neither PG[F.sub.2[alpha]] nor SNAP-mediated changes in cytosolic free [Ca.sup.2+] were affected by SB-203580. We conclude that p38 MAPK contributes to PG[F.sub.2[alpha]]- and hypoxia-induced constriction of rat IPA primarily by antagonizing the underlying [Ca.sup.2+]- desensitizing actions of NO. p38 mitogen-activated protein kinase; pulmonary artery; prostaglandin [F.sub.2[alpha]]; intracellular calcium; calcium sensitization; heat shock protein 27
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- 2005
17. Cholesterol enrichment of rabbit platelets enhances the Ca2+ entry pathway induced by platelet-derived secondary feedback agonists
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Shiraishi, Mitsuya, Tamura, Kazuya, Egoshi, Mina, and Miyamoto, Atsushi
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- 2013
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18. Essential role of rho kinase in the ca2+ Sensitization of Prostaglandin F2α-Induced Contraction of Rabbit Aortae
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Ito, Katsuaki, Shimomura, Erika, Iwanaga, Takahiro, Shiraishi, Mitsuya, Shindo, Kazutoshi, Nakamura, Junji, Nagumo, Hiromitsu, Seto, Minoru, Sasaki, Yasuharu, and Takuwa, Yoh
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- 2003
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19. Vasomotor effects of 5-hydroxytryptamine, histamine, angiotensin II, acetylcholine, noradrenaline, and bradykinin on the cerebral artery of bottlenose dolphin (Tursiops truncatus).
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ISLAM, Md. Zahorul, SAWATARI, Yuji, KOJIMA, Shusuke, KIYAMA, Yusuke, NAKAMURA, Moe, SASAKI, Kyouko, OTSUKA, Mika, OBI, Takeshi, SHIRAISHI, Mitsuya, and MIYAMOTO, Atsushi
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BOTTLENOSE dolphin ,CEREBRAL arteries ,ANGIOTENSIN II ,H2 receptor antagonists ,PROPRANOLOL ,BRADYKININ ,NORADRENALINE - Abstract
From an evolutionary aspect, dolphins share a very close phylogenetic relationship with pigs. Previously, we characterized porcine cerebral artery responsiveness to intrinsic vasoactive substances. Therefore, here, we investigated dolphin (Tursiops truncatus) cerebral artery responsiveness to 5-hydroxytryptamine (5-HT), histamine (His), angiotensin (Ang) II, acetylcholine (ACh), noradrenaline (NA), and bradykinin (BK) to characterize their related receptor subtypes. We also compared dolphin cerebral artery responsiveness with porcine cerebral artery responsiveness. We found that 5-HT and His induced concentration-dependent contraction of the dolphin cerebral artery. Ketanserin (a 5-HT
2 antagonist) and methiothepin (a 5-HT1 and 5-HT2 antagonist) shifted the concentration-response curve for 5-HT to the right. Although diphenhydramine (an H1 antagonist) shifted the concentration-response curve for His to the right, cimetidine (an H2 antagonist) had no such effect. Ang II and ACh did not produce any vasomotor actions. NA induced concentration-dependent relaxation. Propranolol (a β antagonist) shifted the concentration-response curve for NA to the right, whereas phentolamine (an α antagonist) had no significant effect. BK induced relaxation followed by contraction in pre-contracted arteries with intact endothelium. HOE140 (a B2 antagonist) shifted the concentration-response curve for BK to the right, whereas des-Arg9-[Leu8]-BK (a B1 antagonist) had no significant effect. These results suggest that 5-HT1 , 5-HT2 , and H1 receptor subtypes are important in arterial contraction and that β and B2 receptor subtypes modify these contractions to relaxations. The responsiveness of the dolphin cerebral artery is very similar to that of porcine cerebral artery, supporting their evolutionary linkage. [ABSTRACT FROM AUTHOR]- Published
- 2020
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20. Antagonistic Effects of Gingko biloba and Sophora japonica on Cerebral Vasoconstriction in Response to Histamine, 5-Hydroxytryptamine, U46619 and Bradykinin.
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Nguyen, Ha Thi Thanh, Nguyen, Hai Thanh, Islam, Md. Zahorul, Obi, Takeshi, Pothinuch, Pitchaya, Nguyen, Thanh Van, Nguyen, Tuong Manh, Dao, Cuong Van, Shiraishi, Mitsuya, and Miyamoto, Atsushi
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ANALYSIS of variance ,ANIMAL experimentation ,CEREBRAL vasospasm ,GINKGO ,HISTAMINE ,PROBABILITY theory ,PROSTAGLANDINS ,STATISTICS ,SWINE ,T-test (Statistics) ,PLANT extracts ,DATA analysis ,VASOCONSTRICTION ,TREATMENT effectiveness - Abstract
The aim of this study was to evaluate, for the first time, the antagonistic effects of Gingko biloba leaf (GB) and Sophora japonica L. flower bud (SJ) extracts on cerebral vasoconstriction in response to KCl, extracellular Ca, histamine, 5-hydroxytryptamine (5-HT), 9,11-dideoxy-9,11-methanoepoxy prostaglandin (PG) F(U46619) and bradykinin (BK), in order to explain their traditional application for diseases associated with cerebral vasospasm. Isolated porcine basilar arteries (PBA) and endothelial cells from them were used as the study materials. Neither SJ nor GB had any effect on the contractions induced by KCl and extracellular Ca. SJ significantly inhibited the contraction induced by histamine, 5-HT, U46619 and BK, whereas GB inhibited histamine-induced contraction, but had no effects on the contractions induced by 5-HT, U46619 and BK. In the presence of diphenhydramine (a H
1 receptor antagonist), ketanserin (a 5-HT2 receptor antagonist) and ONO-3708 (a thromboxane (TX) A2 /PG receptor antagonist), the inhibitory effects of these extracts on the contractions induced by histamine, 5-HT and U46619 were abolished. SJ significantly inhibited the contractions induced by BK and PGF, but in the presence of ONO-3708 (10 M) had no effect on them. BK enhanced the production of PGF from cultured PBA endothelium cells, and SJ significantly attenuated this enhancement. These results suggest that SJ and GB have a H1 -antagonistic effect, and that SJ also attenuates cerebral vasoconstriction mediated via 5-HT2 and TXA2 /PG receptors. These findings appear to explain why SJ has been used traditionally as a therapeutic medication for cerebral vasospasm after cerebral hemorrhage. [ABSTRACT FROM AUTHOR]- Published
- 2016
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21. Bradykinin induces NO and PGF production via B receptor activation from cultured porcine basilar arterial endothelial cells.
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Islam, Md., Miyagi, Kaori, Matsumoto, Tsukasa, Nguyen, Ha, Yamazaki-Himeno, Emi, Shiraishi, Mitsuya, and Miyamoto, Atsushi
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Our previous in vitro study demonstrated that bradykinin (BK) induced relaxation and contraction of porcine basilar artery (PBA) mediated via activation of endothelial B receptors. The main relaxing and contracting factors appeared to be nitric oxide (NO) and prostaglandin (PG) H, respectively, but not thromboxane A. After obtaining these findings, we succeeded in cultivating endothelial cells isolated from the PBA. Although PGH has different functionally active isoforms, including PGD, PGE, and PGF, we have not yet clarified which of them is responsible for BK-induced contraction. Therefore, we attempted to quantify NO and PG production from cultured porcine basilar arterial endothelial cells (PBAECs) and to identify which of the PGs was involved in this contraction. The cultured PBAECs produced NO spontaneously, and BK enhanced this production in a concentration-dependent manner. The NO synthase inhibitor Nω-nitro- l-arginine (L-NNA) and the B receptor antagonist HOE-140, but not the B receptor antagonist des-Arg, [Leu]-BK, completely abolished it. In a functional study, PGD, PGE, and PGF induced concentration-dependent contractions in isolated porcine basilar arterial rings, the order of maximum contraction being PGF > PGE > PGD. The cultured PBAECs produced PGD, PGE, and PGF spontaneously, and BK significantly enhanced the production of PGF, but not that of PGD and PGE. The B, but not B, antagonist completely abolished the BK-enhanced production of PGF. These results suggest that BK induces production of NO and PGF simultaneously from PBAECs via B receptor activation. [ABSTRACT FROM AUTHOR]
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- 2014
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22. Alteration in MARCKS phosphorylation and expression by methylmercury in SH-SY5Y cells and rat brain.
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Shiraishi, Mitsuya, Hangai, Makoto, Yamamoto, Megumi, Sasaki, Masanori, Tanabe, Atsuhiro, Sasaki, Yasuharu, and Miyamoto, Atsushi
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PROTEIN kinase C , *PHOSPHORYLATION , *METHYLMERCURY , *PROTEIN expression , *CELL survival , *BRAIN physiology , *LABORATORY rats - Abstract
Highlights: [•] Increase in MARCKS phosphorylation was observed in SH-SY5Y cells by MeHg. [•] MARCKS knock-down facilitated loss of cell viability induced by MeHg. [•] Augmentation of MARCKS phosphorylation was observed in MeHg-treated rats. [Copyright &y& Elsevier]
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- 2014
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23. Cholesterol enrichment of rabbit platelets enhances the Ca2+ entry pathway induced by platelet-derived secondary feedback agonists.
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Shiraishi, Mitsuya, Tamura, Kazuya, Egoshi, Mina, and Miyamoto, Atsushi
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ALLERGIES , *LABORATORY rabbits , *BLOOD platelets , *CALCIUM ions , *BLOOD cholesterol , *ADENOSINE diphosphate , *ENZYME-linked immunosorbent assay , *CELLULAR signal transduction - Abstract
Abstract: Aims: Hypersensitivity of platelets due to increased platelet cholesterol levels has been reported in hypercholesterolemia. However, the signaling pathways linking increased platelet reactivity and cholesterol contents are not fully understood. This study aims to determine the direct effect of cholesterol enrichment of platelets on the pathways including Ca2+ mobilization and secondary feedback agonists such as adenosine diphosphate (ADP) and thromboxane A2 (TXA2). Main methods: In vitro cholesterol enrichment of rabbit platelets was performed by incubation with cholesterol complexed with methyl-β-cyclodextrin. Ca2+ mobilization was monitored using platelets loaded with fura-PE3/AM, a fluorescent calcium indicator. Released ATP and TXB2 from platelets were measured by a luciferin–luciferase ATP assay system and a TXB2 ELISA Kit, respectively. Key findings: Cholesterol enrichment of rabbit platelets significantly enhanced Ca2+ mobilization induced by thrombin, accompanying an augmented Ca2+ entry. The augmentation of Ca2+ entry by cholesterol enrichment was significantly suppressed by treatment with inhibitors for secondary feedback agonists. In cholesterol-enriched platelets, the amount of released ATP or TXB2 induced by thrombin was not significantly altered in comparison with control platelets, whereas an increase in [Ca2+]i induced by ADP or U46619, a TXA2 mimetic, was significantly enhanced. Significance: These results suggest that cholesterol enrichment of rabbit platelets results in enhanced Ca2+ mobilization via ADP/TXA2-dependent augmentation of the Ca2+ entry pathway. The results reveal a novel mechanism by which platelet hypersensitivity is regulated by cholesterol contents. [Copyright &y& Elsevier]
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- 2013
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24. MARCKS dephosphorylation is involved in bradykinin-induced neurite outgrowth in neuroblastoma SH-SY5Y cells.
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Tanabe, Atsuhiro, Shiraishi, Mitsuya, Negishi, Manabu, Saito, Naoaki, Tanabe, Mitsuo, and Sasaki, Yasuharu
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BRADYKININ , *DEPHOSPHORYLATION , *NEUROBLASTOMA , *NEURONS , *PROTEIN kinase C , *PHOSPHOLIPASE C , *PAIN management - Abstract
Bradykinin (BK) plays a major role in producing peripheral sensitization in response to peripheral inflammation and in pain transmission in the central nerve system (CNS). Because BK activates protein kinase C (PKC) through phospholipase C (PLC)-β and myristoylated alanine-rich C kinase substrate (MARCKS) has been found to be a substrate of PKC, we explored the possibility that BK could induce MARCKS phosphorylation and regulate its function. BK stimulation induced transient MARCKS phosphorylation on Ser159 with a peak at 1 min in human neuroblastoma SH-SY5Y cells. By contrast, PKC activation by the phorbol ester phorbol 12,13-dibutyrate (PDBu) elicited MARCKS phosphorylation which lasted more than 10 min. Western blotting analyses and glutathione S-transferase (GST) pull-down analyses showed that the phosphorylation by BK was the result of activation of the PKC-dependent RhoA/Rho-associated coiled-coil kinase (ROCK) pathway. Protein phosphatase (PP) 2A inhibitors calyculin A and fostriecin inhibited the dephosphorylation of MARCKS after BK-induced phosphorylation. Moreover, immunoprecipitation analyses showed that PP2A interacts with MARCKS. These results indicated that PP2A is the dominant PP of MARCKS after BK stimulation. We established SH-SY5Y cell lines expressing wild-type MARCKS and unphosphorylatable MARCKS, and cell morphology changes after cell stimulation were studied. PDBu induced lamellipodia formation on the neuroblastoma cell line SH-SY5Y and the morphology was sustained, whereas BK induced neurite outgrowth of the cells via lamellipodia-like actin accumulation that depended on transient MARCKS phosphorylation. Thus these findings show a novel BK signal cascade-that is, BK promotes neurite outgrowth through transient MARCKS phosphorylation involving the PKC-dependent RhoA/ROCK pathway and PP2A in a neuroblastoma cell line. J. Cell. Physiol. 227: 618-629, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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25. Modulation of Rabbit Platelet Aggregation and Calcium Mobilization by Platelet Cholesterol Content.
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SHIRAISHI, Mitsuya, TANI, Eisuke, and MIYAMOTO, Atsushi
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CHOLESTEROL ,BLOOD platelet activation ,PLATELET activating factor ,RABBITS ,HYPERCHOLESTEREMIA ,BLOOD lipoproteins ,BLOOD cholesterol - Abstract
The article focuses on a study which determined the direct role of cholesterol on rabbit platelet activation and examined the effect of in vitro modulation of cholesterol content on platelet activation. It was observed that cholesterol repletion in platelets restored the inhibition of thrombin-induced aggregation in cholesterol depleted platelets. Study results suggested that cholesterol plays an important role in regulating rabbit platelet activation, and provided fundamental information regarding hypercholesterolemia-mediated effects on cells in the rabbit model.
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- 2010
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26. MARCKS regulates lamellipodia formation induced by IGF-I via association with PIP2 and β-actin at membrane microdomains.
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YAMAGUCHI, HIROKI, SHIRAISHI, MITSUYA, FUKAMI, KIYOKO, TANABE, ATSUHIRO, IKEDA-MATSUO, YURI, NAITO, YASUHITO, and SASAKI, YASUHARU
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ALANINE , *PROTEIN kinases , *ACTIN , *LIPIDS , *CYTOLOGY , *PHYSIOLOGY - Abstract
Myristoylated alanine-rich C kinase substrate (MARCKS) is considered to participate in formation of F-actin-based lamellipodia, which represents the first stage of neurite formation. However, the mechanism of how MARCKS is involved in lamellipodia formation is not precisely unknown. Using SH-SY5Y cells, we demonstrated here that MARCKS was translocated from cytosol to detergent-resistant membrane microdomains, known as lipid rafts, within 30 min after insulin-like growth factor-I (IGF-I) stimulation, which was accompanied by MARCKS dephosphorylation, β-actin accumulation in lipid rafts, and lamellipodia formation. The protein kinase C inhibitor, Ro-31-8220, and Rho-kinase inhibitors, HA1077 and Y27632, themselves decreased basal phosphorylation levels of MARCKS and coincidently elicited translocation of MARCKS to lipid rafts. On the other hand, the phosphoinositide 3-kinase inhibitor, LY294002, abolished IGF-I-induced dephosphorylation, translocation of MARCKS to lipid rafts, and lamellipodia formation. Treatment of cells with neomycin, a PIP2-masking reagent, attenuated the translocation of MARCKS to lipid rafts and the lamellipodia formation induced by IGF-I, although dephosphorylation of MARCKS was not affected. Immunocytochemical and immunoprecipitation analysis indicated that IGF-I stimulation induced the translocation of MARCKS to lipid rafts in the edge of lamellipodia and formation of the complex with PIP2. Moreover, we demonstrated that knockdown of endogenous MARCKS resulted in significant attenuation of IGF-I-induced β-actin accumulation in the lipid rafts and lamellipodia formation. These results suggest a novel role for MARCKS in lamellipodia formation induced by IGF-I via the translocation of MARCKS, association with PIP2, and accumulation of β-actin in the membrane microdomains. J. Cell. Physiol. 220: 748–755, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
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- 2009
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27. Unphosphorylated MARCKS is involved in neurite initiation induced by insulin-like growth factor-I in SH-SY5Y cells.
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Shiraishi, Mitsuya, Tanabe, Atsuhiro, Saito, Naoaki, and Sasaki, Yasuharu
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ALANINE , *CELL differentiation , *PHOSPHORYLATION , *CELLS , *SOMATOMEDIN , *PHOSPHOINOSITIDES - Abstract
Myristoylated alanine-rich C kinase substrate (MARCKS) has been suggested to be involved in various aspects of neuronal cell differentiation, including neurite outgrowth. However, the precise mechanisms by which MARCKS phosphorylation is regulated, and how MARCKS contributes to neurite outgrowth, are poorly understood. Here, we found that treatment of SH-SY5Y cells with insulin-like growth factor-I (IGF-I) induced a rapid and transient decrease in the level of phosphorylated MARCKS (P-MARCKS) to below the basal level. The decrease in P-MARCKS induced by IGF-I was blocked by pretreatment of cells with phosphoinositide 3-kinase (PI3K) inhibitors, LY294002 and wortmannin. A decrease in P-MARCKS was also observed in cells treated with a Rho-dependent kinase (ROCK) inhibitor, Y27632. Furthermore, IGF-I induced transient inactivation of RhoA, an upstream effector of ROCK. We showed that MARCKS was translocated to the membrane and colocalized with F-actin at the lamellipodia and the tips of neurites in the cells stimulated with IGF-I. Finally, overexpression of wild-type MARCKS or an unphosphorylatable mutant of MARCKS enhanced the number of neurite-bearing cells relative to vector-transfected cells. Taken together, these findings suggest that unphosphorylated MARCKS is involved in neurite initiation, and highlight the important role played by MARCKS in organization of the actin cytoskeleton. J. Cell. Physiol. 209: 1029–1038, 2006. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
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- 2006
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28. Linalyl Acetate as a Major Ingredient of Lavender Essential Oil Relaxes the Rabbit Vascular Smooth Muscle through Dephosphorylation of Myosin Light Chain.
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Koto, Ruriko, Imamura, Masatoshi, Watanabe, Chie, Obayashi, Satoshi, Shiraishi, Mitsuya, Sasaki, Yasuharu, and Azuma, Hiroshi
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- 2006
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29. Modulation of PGF2α and hypoxia-induced contraction of rat intrapulmonary artery by p38 MAPK inhibition: a nitric oxide-dependent mechanism.
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Knock, Greg A., De Silva, Anushika S., Snetkov, Vladimir A., Siow, Richard, Thomas, Gavin D., Shiraishi, Mitsuya, Walsh, Michael P., Ward, Jeremy P. T., and Aaronson, Philip I.
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PROTEIN kinases ,SMOOTH muscle ,PROSTAGLANDINS ,MITOGENS ,PULMONARY artery diseases - Abstract
The mechanisms through which p38 mitogen-activated protein kinase (p38 MAPK) is involved in smooth muscle contraction remain largely unresolved. We examined the role of p38 MAPK in prostaglandin F
2α , (PGF2α )-induced vasoconstriction and in hypoxic pulmonary vasoconstriction (HPV) of rat small intrapulmonary arteries (IPA). The p38 MAPK inhibitors SB-203580 and SB-202190 strongly inhibited PGF2α -induced vasoconstriction, with IC50 s of 1.6 and 1.2 µM, whereas the inactive analog SB-202474 was ∼30-fold less potent. Both transient and sustained phases of HPV were suppressed by SB-203580, but not by SB-202474 (both 2 µM). Western blot analysis revealed that PGF2α (20 µM) increased phosphorylation of p38 MAPK and of heat shock protein 27 (HSP27), and this was abolished by SB-203580 but not by SB-202474 (both 2 µM). Endothelial denudation or blockade of endothelial nitric oxide (NO) synthase with Nω -nitro-L-arginine methyl ester (L-NAME) significantly suppressed the relaxation of PGF2α -constricted IPA by SB-203580, but not by SB-202474. Similarly, the inhibition of HPV by SB-203580 was prevented by prior treatment with L-NAME. SB-203580 (2 µM), but not SB-202474, enhanced relaxation-induced by the NO donor S-nitroso-N-acetylpenicillamine (SNAP) in endothelium-denuded IPA constricted with PGF2α . In α-toxin-permeabilized IPA, SB-203580-induced relaxation occurred in the presence but not the absence of the NO donor sodium nitroprusside (SNP); SB-202474 was without effect even in the presence of SNP. In intact IPA, neither PGF2α - nor SNAP-mediated changes in cytosolic free Ca2+ were affected by SB-203580. We conclude that p38 MAPK contributes to PGF2α - and hypoxia-induced constriction of rat IPA primarily by antagonizing the underlying Ca2+ -desensitizing actions of NO. [ABSTRACT FROM AUTHOR]- Published
- 2005
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30. Essential role of rho kinase in the ca2+ Sensitization of Prostaglandin F2α-Induced Contraction of Rabbit Aortae.
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Ito, Katsuaki, Shimomura, Erika, Iwanaga, Takahiro, Shiraishi, Mitsuya, Shindo, Kazutoshi, Nakamura, Junji, Nagumo, Hiromitsu, Seto, Minoru, Sasaki, Yasuharu, and Takuwa, Yoh
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- 2003
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31. Myosin heavy chain expression in renal afferent and efferent arterioles: relationship to contractile kinetics and function.
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Shiraishi, Mitsuya, Wang, Xuemei, Walsh, Michael P., Kargacin, Gary, Loutzenhiser, Kathy, and Loutzenhiser, Rodger
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AFFERENT pathways , *EFFERENT pathways , *ANGIOTENSINS , *MYOSIN , *MUSCLE proteins - Abstract
Compares the contractile kinetics of the afferent and efferent arterioles. Time courses for angiotensin II- and norepinephrine-induced vasoconstriction of renal afferent and efferent arterioles; Methods used; Expression patterns for myosin heavy chain (MHC) 1 and MHC-2 isoforms.
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- 2003
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32. Histamine-induced modulation of vascular tone in the isolated chicken basilar artery: A possible involvement of endothelium
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Okuno, Tadatsune, Yabuki, Akira, Shiraishi, Mitsuya, Obi, Takeshi, and Miyamoto, Atsushi
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HISTAMINE , *BIOGENIC amines , *IMIDAZOLES , *MUSCLE cells , *SMOOTH muscle , *SEROTONIN - Abstract
Abstract: We investigated the histamine responsiveness of basilar arterial rings isolated from chicken. We also examined whether endothelial cells were involved in the histamine responsiveness and in resting vascular tone. Histamine induced concentration-dependent relaxations under condition of precontraction by 5-hydroxytryptamine. The concentration–response curve for histamine was shifted to the right by diphenhydramine (a H1 receptor antagonist), cimetidine (a H2 receptor antagonist) and Nω-nitro-l-arginine (l-NNA, a nitric oxide synthase inhibitor); however, indomethacin (a cyclooxygenase inhibitor) had no significant effect on it. Treatment with l-NNA shifted the concentration–response curve of histamine to the right in the presence of cimetidine, but not in the presence of diphenhydramine. Treatment with cimetidine shifted the concentration–response curve of histamine to the right in the presence of diphenhydramine. l-NNA induced a contraction but indomethacin had no effect on the resting vascular tone. These results suggest that histamine-induced relaxation is mediated via activation of H1 receptors located on endothelial cells and H2 receptors located on smooth muscle cells. The main relaxing factor released from endothelial cells is probably nitric oxide. The resting vascular tone was modulated by spontaneously released nitric oxide, but not by prostaglandins or thromboxane A2. [Copyright &y& Elsevier]
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- 2008
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33. Involvement of beta3-adrenergic receptors in relaxation mediated by nitric oxide in chicken basilar artery.
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Wu, Siyuan, Ootawa, Tomoki, Sekio, Ryoya, Smith, Henry, Islam, Md. Zahorul, Uno, Yasuhiro, Shiraishi, Mitsuya, and Miyamoto, Atsushi
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BASILAR artery , *NITRIC oxide , *ADRENERGIC receptors , *CHICKENS , *ANIMAL species , *NORADRENALINE - Abstract
The response of basilar arteries to noradrenaline varies among many animal species, but remains little studied in poultry. Accordingly, we aimed to characterize the adrenergic receptor (AR) subtypes that modulate vascular response in basilar arteries in the chicken, with isometric recording of arterial ring tension using an organ bath. We demonstrated the presence of both alpha and beta (α and β) receptor subtypes through evaluating the response to noradrenaline, with and without a range of β-AR and α-AR antagonists. The concentration-dependent relaxations then induced by a range of β-AR agonists indicated a potency ranking of isoproterenol > noradrenaline > adrenaline > procaterol. We then investigated the effects of β-AR antagonists that attenuate the effect of isoproterenol (propranolol for β 1,2,3 -ARs, atenolol for β 1 -ARs, butoxamine for β 2 -ARs, and SR 59230A for β 3 -ARs), with Schild regression analysis, ascertaining multiple β-AR subtypes, with neither the β 1 -AR nor the β 2 -AR as the dominant subtype. SR 59230A was the only antagonist to yield a pA 2 value (7.52) close to the reported equivalent for the relevant receptor subtype. Furthermore, treatment with SR 58611 (a β 3 -AR agonist) induced relaxation, which was inhibited (P < 0.01) by L-NNA and SR 59230A. Additionally, treating basilar arterial strips (containing endothelium) with SR 58611 induced nitric oxide (NO) production, which was inhibited (P < 0.01) by L-NNA and SR 59230A. Based on this first characterization of AR subtypes in chicken basilar arteries (to our knowledge), we suggest that α- and β-ARs are involved in contraction and relaxation, and that β 3 -ARs, especially those on the endothelium, may play an important role in vasodilation via NO release. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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34. Pharmacological characteristics of Artemisia vulgaris L. in isolated porcine basilar artery.
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Nguyen, Ha Thi Thanh, Nguyen, Hai Thanh, Islam, Md. Zahorul, Obi, Takeshi, Pothinuch, Pitchaya, Zar, Phyu Phyu Khine, Hou, De Xing, Van Nguyen, Thanh, Nguyen, Tuong Manh, Van Dao, Cuong, Shiraishi, Mitsuya, and Miyamoto, Atsushi
- Abstract
Ethnopharmacological relevance In Vietnamese traditional herbalism, there are conflicting opinions about the effect of Artemisia vulgaris L. (AVL, English name: mugwort) on hypertension. Some ethnic doctors recommend the use of AVL for treatment of hypertension, whereas others advise against it. The purpose of this study was to clarify the pharmacological characteristics of AVL in isolated arteries to explain the conflicts surrounding the use of AVL for treatment of hypertension. Materials and methods We initially performed a functional study using an organ bath system to investigate the effect of AVL extract on isolated porcine basilar artery. We then measured the change in intracellular free Ca 2+ concentration elicited by AVL using cultured smooth muscle cells loaded with the Ca 2+ indicator fluo-4. Finally, using HPLC, we determined the active components in AVL. Results and discussion AVL induced vasoconstriction at resting tension, and endothelial removal enhanced this effect significantly. Pretreatment with PD123319 (an AT 2 receptor antagonist), Nω - nitro - L - arginine (a nitric oxide synthase inhibitor), or both, also enhanced this effect. AVL-induced contraction was competitively inhibited by methiothepin (a 5-HT 1 and 5-HT 2 receptor antagonist) in the presence of ketanserin (a 5-HT 2 receptor antagonist). Removal of extracellular calcium with nifedipine (an L-type Ca 2+ channel blocker) or ruthenium red (a ryanodine receptor blocker) significantly reduced AVL-induced contraction, whereas losartan (an AT 1 receptor antagonist) and diphenhydramine (a H 1 receptor antagonist) had no effect on this contraction. AVL increased the intracellular free Ca 2+ concentration in cultured cells, and this increment was inhibited by methiothepin. HPLC analysis revealed that the retention time of the first peak in the AVL profile was similar to that of the 5-HT standard, and that addition of 5-HT to the AVL sample enhanced this peak. On the other hand, AVL induced endothelium-independent relaxation under precontracted conditions with 60 mM KCl. Captopril (an angiotensin converting enzyme inhibitor), atenolol (a β 1 receptor antagonist) and cimetidine (a H 2 receptor antagonist) had no effect on this relaxation. In Ca 2+ -free 60 mM KCl-containing solution, pretreatment with AVL significantly inhibited CaCl 2 -induced contraction. Conclusion For the first time, the present study has demonstrated that AVL has two opposite effects, contraction and relaxation, on isolated artery, which may help to explain the conflicting indications for AVL in traditional herbalism. 5-HT is a significant factor affecting artery contraction in the presence of AVL. [ABSTRACT FROM AUTHOR]
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- 2016
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35. Nitric oxide-dependent hypotensive effects of wax gourd juice
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Nakashima, Miki, Shigekuni, Yukiko, Obi, Takeshi, Shiraishi, Mitsuya, Miyamoto, Atsushi, Yamasaki, Hideo, Etoh, Takeomi, and Iwai, Sumio
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ALTERNATIVE medicine , *ANIMAL experimentation , *AORTA , *BIOPHYSICS , *BLOOD pressure measurement , *VASODILATION , *DOSE-effect relationship in pharmacology , *CARDIAC contraction , *ANTIHYPERTENSIVE agents , *INTRAVENOUS therapy , *RESEARCH methodology , *MEDICINAL plants , *NITRIC oxide , *RATS , *VEGETABLES , *PLANT extracts , *PHARMACODYNAMICS - Abstract
Abstract: Ethnopharmacological relevance: The wax gourd (Benincasa hispida (Thunb) Cong.) is a long-season vegetable that has been used in traditional Chinese medicine to treat high blood pressure. However, precise details of its effect and the mechanism of action involved are still lacking. Materials and methods: Ten-fold-condensed wax gourd juice was used for the experiments. We measured (1) blood pressure of anesthetized normal Wistar rats in vivo, (2) isolated rat aortic contraction and relaxation, and (3) nitric oxide production from cultured porcine endothelial cells. The rats mentioned had not been treated with the investigational medicine. Results: Intravenous injection of the juice produced a dose-dependent decrease in blood pressure. Treatment with the juice induced concentration-dependent relaxation of isolated rat aortic rings that had been precontracted with noradrenaline. The relaxation induced by the juice was strongly inhibited by treatment with the nitric oxide (NO) synthase inhibitor NG-nitro-l-arginine methyl ester hydrochloride (l-NAME) or endothelial denudation. Treatment with the juice produced NO from cultured porcine aortic endothelial cells. This NO production was significantly inhibited by l-NAME. Conclusions: The present findings suggest that wax gourd juice exerts a hypotensive effect via endothelium-dependent vasodilation. The main endothelium-derived relaxing factor involved might be NO. [Copyright &y& Elsevier]
- Published
- 2011
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36. Vasomotor effects of noradrenaline, acetylcholine, histamine, 5-hydroxytryptamine and bradykinin on snake (Trimeresurus flavoviridis) basilar arteries
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Yoshinaga, Narihiro, Okuno, Tadatune, Watanabe, Yutaka, Matsumoto, Tsukasa, Shiraishi, Mitsuya, Obi, Takeshi, Yabuki, Akira, and Miyamoto, Atsushi
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NORADRENALINE , *ACETYLCHOLINE , *HISTAMINE , *BRADYKININ , *PHENTOLAMINE , *ARTERIES , *RATTLESNAKES - Abstract
Abstract: We investigated the responsiveness of basilar arterial rings isolated from snakes to noradrenaline (NA), acetylcholine (ACh), histamine (His), 5-hydroxytryptamine (5-HT), mammalian bradykinin (BK) and rattlesnake BK. We also examined whether endothelial cells were involved in the responsiveness to ACh, BK, rattlesnake BK and in their resting vascular tone. NA and 5-HT induced concentration-dependent contractions. The cumulative concentration response curves of NA and 5-HT were shifted to the right in parallel by phentolamine (an α antagonist) and methiothepin (a 5-HT1 and 5-HT2 antagonist), respectively. However, ketanserin (a 5-HT2 antagonist) had no effect on the cumulative concentration response curve of 5-HT. His, ACh, BK and rattlesnake BK had no effect on resting vascular tone; however, rattlesnake BK and sodium nitroprusside relaxed arteries precontracted by 5-HT. The rattlesnake BK-induced relaxations were almost abolished by L-nitro arginine (L-NA, a nitric oxide synthase inhibitor). L-NA and indomethacin (a cyclooxygenase inhibitor) had no effect on resting vascular tone or on precontracted arteries. These results suggest that α and 5-HT1 receptor subtypes might be important in arterial contraction. Endothelial cells might play an important role in the responsiveness of snake basilar arteries to rattlesnake BK, but they might not be involved in the responsiveness to ACh, BK and in resting vascular tone. [Copyright &y& Elsevier]
- Published
- 2007
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