| Project/Area Number |
61570099
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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 |
General pharmacology
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| Research Institution | Mie University |
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Principal Investigator |
TANAKA Toshio Mie University,School of Medicine, Lecturer, 医学部, 講師 (00135443)
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| Co-Investigator(Kenkyū-buntansha) |
NAKA Michiko Mie University School of Medicine,Assistant, 医学部, 助手 (10093139)
日高 弘義 三重大学, 医学部, 教授 (80100171)
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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 |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1987: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1986: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Intracellular Calcium-Receptine Protein / Molecular Pharmacology / Calmodulin / Protein Kinase C / Calcium-dependent Protease / Calpain / Myosin Light Chain Kinase / カルモデュリン阻害剤 / カルシウムチャンネルブロッカー / トロポニンC / パルブアルブミン / カルモデュリン依存性酵素 |
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| Research Abstract |
Major intracellular calcium-binding protein in vascular smooth muscle is calmodulin, which act through its stimulation of myosin light chain kinase. We found two types of new calmodulin antagonists in this study. One is HT-74,which is a calmodulin antagonist and binds to calmodulin in a manner different from that heretofore reported. Another one is bepridil and it is an antianginal, antiarrhythmic agent with calcium antagonistic properties and is found to bind to calmodulin in the presence of calcium ion and potently inhibit the myosin light chain phosphorylation. These compound may be useful to study calmodulin-dependent calcium signaling. Moreover, we envestigated the interaction between calcium, calmodulin-dependent myosin light chain kinase and calcium-dependent protease (calpain) and the relationship between the myosin light chain kinase and protein kinase C by using isoquinolinesulfonamide derivatives. These results suggest that the calcium-activated proteases may recognize the conformational change of smooth muscle myosin light chain kinase induced by Ca^<2+>-calmodulin complex. And these isoquinolinesulfonamide derivatives should prove to be useful tools for distinguishing between the biological function of Ca^<2+>-activated, phsopholipid-dependent, and calcium, calmodulin-dependent myosin light chain phosphorylation.
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