| Project/Area Number |
61570416
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kobe University |
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Principal Investigator |
YOKOYAMA Mitsuhiro Kobe University School of Medicine, associate professor, 医学部, 助教授 (40135794)
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| Co-Investigator(Kenkyū-buntansha) |
山崎 享 神戸大学, 医学部・附属病院, 医員
TAKEUCHI Motoshi Kobe University Hospital, assistant professor, 医学部附属病院, 助手 (50188166)
矢谷 暁人 神戸大学, 医学部・附属病院, 医員
市川 靖典 神戸大学, 医学部・附属病院, 医員
AKITA Hozuka Kobe University School of Medicine, assistant professor, 医学部, 助手 (60175792)
YATANI Akihito Kobe University Hospital, medical staff
ICHIKAWA Yasunori Kobe University Hospital, medical staff
YAMASAKI Tohru Kobe University Hospital, medical staff
山崎 亨 神戸大学, 医学部, 医員
藤井 隆 神戸大学, 医学部, 医員
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Vascular Smooth Muscle Cells / Serotonin / Norepinephrine / Histamine / Inositol phospholipids / Protein kinase C / Phorbol esters / ホルボール エステル / 血管平滑筋 / ホスファチジールイノシトール代謝 / Cキナーゼ / ホルボールエステル / 血管収縮 / 血管拡張 |
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| Research Abstract |
Monoamines such as norepinephrine, serotonin, and histamine are potent vasoconstrictors. The goal of this study was to examine receptor-mediated hydrolysis of membrane inositol phospholipids and its regulation, which results in the generation of two intracellular second messengers, inositol 1,4,5-trisphosphate(IP3) and diacylglycerol in vascular smooth muscles. We adopted ^<32>Pi labeling method in intact aortic ring preparatin and ^3H-inositol labeling method in cultured aortic smooth muscle cells obtained from rabbits. These amines stimulated phosphoinositides breakdown dose-dependently through <alpha>^2-adrenergic, 5HT2 and H1 receptor activations. Phosphatidylinositol labeling curve and contractin curve for each agonist were similar. We found that a guanine nucleotide inhibitory (Gi) protein coupled 5HT receptor to phospholipase C and phorbol esters such as TPA modulated 5HT-stimu-lated hydrolysis of inositol phospholipids. Specific regulatory mechanisms for each agonist may exist between receptor activatin and phosphoinositides breakdown, as early degradation and resynthesis of phosphoinositides (PI,PIP and PIP2) in response to each agonist were different. Phosphoinositides labeling and the contractin induced by these amines were differently coupled with the influx of extracellular Ca^<++> influx. Receptor-mediated phosphoinositides breakdown was regulated by cyclic nucleotides ( cyclic AMP and cyclic GMP ). Phorbol esters such as TPA induced a sustained contraction of isolated rabbit aorta that was entirely dependent on intracellular Ca^<++>. TPA inhibited the endothelium dependent relaxation induced by acetylcholine, but not the nitroglycerin-induced relaxation.
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