1998 Fiscal Year Final Research Report Summary
Regulatory mechanisms of cytosolic ion transients during cell cycle progression in vascular endothelial and smooth muscle cells
| Project/Area Number |
08457211
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Yamaguchi University |
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Principal Investigator |
KOBAYASHI Sei Yamaguchi University, School of Medicine, Professor, 医学部, 教授 (80225515)
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| Project Period (FY) |
1996 – 1998
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| Keywords | Cell Cycle / Cell Proliferation / Blood Vessel / Vasocontraction / Vasorelaxation / Calcium Ion / Smooth Muscle Cells / Vasoactive Substances |
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| Research Abstract |
The following results were obtained :
1. CELL PROLIFERATION OF VASCULAR SMOOTH MUSCLE CELLS AND ITS RELATION TO THE CELLULAR FUNCTION.I developed the method to determine both the phase of the cell cycIe and cell function of the same single-cell of vascular smooth muscle cells (VSMCs) in primary culture. It was found that : (1) the expression of types of Ca^<2+> channels changes with the cell cycle ; (2) the activation of P2u receptor stimulates the cell cycle progression from the G1 to the S/M phases, but not from the G0 to G1 phase, whereas it elevates cytosolic Ca^<2+> concentration ([Ca^<2+>] i) in the VSMCs at the G0 and C1 phases equally ; and (3) Ca^<2+> channel blockers differently affect Ca^<2+> transients and cell cycle progression in VSMCs.
2. VASCULAR CONTRACTION.(1) Differential mechanisms ([Ca^<2+>]i-force relation, Ca^<2+> sensitivity of contractile apparatus, and mRNA expression) of vasorelaxation by vasodilators were elucidated. (2) It was found that resting load regulates [Ca^<2+>] i-force relation of the contraction of vascular smooth muscle. (3) It was found that Rho-kinase induces myosin light chain phosphorylation and Ca^<2+>-independent contraction, which is independent of the Ca^<2+>- calmodulin-MLCK pathway. (4) Bradykinin was shown to elevate [Ca^<2+>] i and Ca^<2+> sensitivity of contractile apparatus, as mediated by the activation of the B2 receptor and G-proteins. (5) It was demonstrated that tyrosine kinase Inhibitor markedly suppressed the development of coronary lesions in pig in vivo. (6) Down-regulation of endotihelin B receptors was observed in autogenous saphenous veins grafted into the arterial circulation. (7) It was suggested that endothelins may be autocrine and/or paracrine transmitters 'to regulate the contraction of airway smooth muscle.
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