| Project/Area Number |
10672046
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Department of Pharmacology, Faculty op Pharmaceutical Sciences, University of Shizuoka |
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Principal Investigator |
NAKAYAMA Koichi Ph. D., Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Shizuoka, Professor and Head., 薬学部, 教授 (50112769)
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| Co-Investigator(Kenkyū-buntansha) |
OBARA Kazuo Ph. D., Lecturer, 薬学部, 講師 (60117611)
TANABE Yoshiyuki Ph. D., Assistant to Professor Nakayama, 薬学部, 助手 (10275109)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | hemodynamic stress / mechanotransduction / myogenic contraction / cerebral artery / caveola / caveolin / cellular signaling / cerebral vasospasm / カルシウム動態 / インテグリン / チロシンキナーゼ / 脳動脈 |
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| Research Abstract |
Caveolae, identified as flask-shaped invaginations on the surface of the plasma membrane, have been considered to be hot spots for cell signaling, A variety of functional proteins, including ion channels, are localized in caveolae, and assembled with each other, resulting in expression of biological and pharmacological functions. We summarize herewith our results as following :
1) Mechanotransduction and tyrosine kinase / tyrosine phosphorylation in cerebral and pulmonary arteries :
The mechanisms of pressure-induced myogenic contraction was studied with regard to tyrosine phosphrylation were studied. Intracellular Ca concentration and vessel diameter were simultaneously measured. Furthermore, we tried to detect immunocytochemically in situ total tyrosine phosphorylation level and activity of pp60src in the arteries.
2) Intracellular localization of protein kinase C isoforms in the contractile potentiation of coronary artery by agonistic stimuli and experimental cerebral vasospasm :
Endoth
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elin 1 at a low concentration of 10-100pM potentiated 5-hydroxytryptamine-induced contraction of porcine coronary artery, which was consistent with translocation of protein kinase (PKC) a and d isoforms. Canine model of experimental cerebral vasospasm induced by injection of autologous blood injected into cisterna magna was also investigated with regard to PKC isoforms. PKC d was translocated to the membrane fraction during the development of the vasospasm, and PKC a was tanslocated in the late phase of established vasospasm. PKC a and d isoforms were densely located in caveolin-rich fraction. Furthermore, we suggest that mechanical stress such as stretch induces activation and down-regulation of PKC a in caveolae.
3) Discussion and future development :
The present results suggest that tyrosine kinase such as src family and PKC a and d isoforms assembles in caveolae and play a regulatory role in the expression of biological function such as contraction. We will improve the methods of immunocytochemical in situ detection and immunoprecipitation in the cardiovascular system. We will also develop a new pharmacological study aiming to detect simultaneously biological function and molecular dynamics in situ. Less
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