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Small GTP-Binding Protein and Signaling on Vascular Smooth Muscle Contraction

Research Project

Project/Area Number 09670100
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionNagoya City University

Principal Investigator

KAWABE Mayumi  Nagoya City University, Medical School, Research Associate, 医学部, 助手 (90117862)

Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Keywordssmooth muscle / Rho / Translocation / Rho kinase / ACh / myosin light chain phosphorylation / Lysophosphatidic acid / Contraction / 腸管平滑筋 / Rock / High K^+ / リゾフォスファチジン酸 / チロシンキナーゼ
Research Abstract

It is well known that signaling on smooth muscle contraction is regulated by level of myosin light chain (MLC) phosphorylation. The level of MLC phosphorylation is determined by the balance of activities of both myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP). The activity of MLCK is dependent on Ca^<2+>/ca1modulin, whereas that of MLCP is regulated through Rho/Rho kinase. We studied a role of Rho/Rho kinase in smooth muscle contraction signaling using intact guinea-pig ileal smooth muscle.
1. Lysophosphaticic acid (LPA), an activator of Rho, induced feeble, but sustained contraction in ileal longitudinal smooth muscle and taenia coli, without marked increases in MLC phosphorylation.
2. Rho kinase inhibitor Y-27632 (1 micromol) inhibited LPA-induced contraction almost completely.
3. Y-27632 (10 micromol) slightly inhibited ACh (1 micromol) -induced contraction at 2 min after administration of the agonist. On the other hand, the inhibitor (10 micromol) showed no effects on high K^+ (50 mM) -induced contraction.
4. At 1 or 10 min after the stimulation of ACh, high K^+ solution or LPA, rho protein in thecytosol fraction decreased without significant changes in rho protein contents in detergent-soluble fraction.
These results indicate that contacting agents (LPA, ACh and high K^+) induced translocation of rho protein in intact smooth muscle of ileum. However, the feeble contraction by the Rho activator and the inhibition of their contractions by the specific inhibitor of Rho kinase suggest that the role of Rho/Rho kinase on the contraction of intact guinea-pig ileal smooth muscle is not so much important.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] M.Mori and H.Tsushima: "Phosphorylation of myosin light chain by lysophosphatidic acid in guinea-pig smooth muscle." Japanese Journal of Pharmacology. 76. 303 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Mori and H.Tsushima: "Role of Rho proteins in smooth muscle contraction of intact guinea-pig ileum." Japanese Journal of Pharmacology. 79. 269 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Mori and H.Tsushima: "Phosphorylation of myosin light chain by lysophosphatidic acid in guinea-pig smooth muscle." Japanese Journal of Pharmacology. 76(Suppl.I). 303 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Mori and H.Tsushima: "Role of Rho proteins in smooth muscle contraction of intact guinea-pig ileum" Japanese Journal of Pharmacology. 79(Suppl.I). 269 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary

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Published: 1997-04-01   Modified: 2016-04-21  

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