| Project/Area Number |
07672460
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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 |
応用薬理学・医療系薬学
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| Research Institution | Mie University |
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Principal Investigator |
NAKA Michiko Faculty of Medicine, Mie University, Assistant, 医学部, 助手 (10093139)
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| Co-Investigator(Kenkyū-buntansha) |
向井 淳 三重大学, 医学部, 助手 (70263019)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Calponin / Smooth muscle / Calcium ion / Phosphorylation / Contraction / PKC / Actin / Ca2+-sensitivity / プロテインキナーゼC / アクチン結合 / 繰り返し構造 / 冠状動脈 / 血管収縮 / シグナル伝達 |
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| Research Abstract |
The contractile response in smooth muscle cells is regulated by changes in intracellular calcium ion concentrations and depends upon myosin and actin interaction. Many examples of dissociation between intracellular free Ca2+ concentration levels, myosin light chain phosphorylation levels, cross-bridge cycling rates and force levels have been reported. These results strongly implicate either the existence of an agonist-induced increase in the calcium-sensitivity of the contractile proteins or a calcium-independent process. We investigated the calponin phosphorylation during endothelin-1 or PDBu stimulation of intact strips of porcine coronary artery. Stimulation by endothelin-1 or phorbol 12,13-dibutylate (PDBu) resulted in a significant increase of 32P incorporation into the calponin in association with development of force. Calponin is an abundant thin filament-associated smooth muscle protein that has been implicated to play a role in the regulation of smooth muscle. Recently, we fou
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nd that smooth muscle calponin is an excellent substrate for protein kinase C and the phosphorylation reduced the binding of calponin to F-actin and tropomyosin. The first repeated motif contained the preferred site of phosphorylation by PKC and phosphorylation of this motif was subjected to competitive inhibition by actin. In addition, the binding to actin of calponin was also inhibited by the phosphorylation of calponin in a competitive fashion, an indication that the actin-binding region of calponinshould be adjacent to the preferred site of phosphorylation by PKC.In permeabilized smooth muscle, synthetic peptides that corresponded to the first repeated motif enhanced Ca2+-induced contraction without a corresponding increase in the extent of phosphorylation of myosin light chain These results suggest that calponin decreases the sensitivity of smooth muscle contraction to calcium ion at a given level of myosin light chain phosphorylation. Under physiological conditions, calponin acts in a negative fashion on smooth muscle contraction which is initiated by myosin phosphorylation-dependent mechanisms and thus lowers the myofilament Ca2+-sensitivity. Less
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