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Regulation of smooth muscle contraction through remodeling of actin filaments

Research Project

Project/Area Number 17500277
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurophysiology and muscle physiology
Research InstitutionTokyo Medical University

Principal Investigator

WATANABE Masaru  Tokyo Medical University, Department of Physiology, Lecturer, 医学部, 講師 (60191798)

Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordssmooth muscle / actin filaments / remodeling / skinned preparation / blebbistatin / phenoxazine / gelsolin / 筋フィラメント / ブレビスタチン
Research Abstract

1)Mechanism of the inhibitory effects of Phx-1 on the smooth muscle contraction To elucidate the mechanisms of relaxing effect of 2-amino-4,4 a-dihydro-4 a-7-dimethyl-3H-phenoxazine-3-one (Phx-1) on the smooth muscle preparations, we investigated effects of Phx-1 on the contraction of both intact and skinned (cell membrane peremeabilized) preparations from guinea pig tenia cecum. In intact preparations, Phx-1 concentration-dependently suppressed the contraction induced by either acetycholine(ACh) or high-K+ with the IC50 value estimated at around 100 pM. Similar inhibitory actions of Phx-1 on force were observed in intracellular Ca store depleted preparations. In the cell membrane depolarized preparations in the absence of extracellular Ca, however, Phx-1 had little effects on the caffeine-or ACh-induced contraction. In skinned preparations, Phx-1 suppressed the Ca^<2+->induced contraction at concentrations higher than 100 μM. These results suggest that Phx-1 seems to have direct inhib … More itory effect on the actin filaments organization, although inhibitory effect, of the Phx-1 on the Ca^<2+>-influx is much stronger.
2)Contractile filaments remodeling by blebbistatin, a potent inhibitor of myosin II We studied the effects of blebbistatin, a potent inhibitor of myosin II on the mechanical and structural properties of beta escin skinned taenia cecum. Blebbistatin inhibited both Ca^<2+> induced contraction with only little effects on the Ca^<2+> sensitivity for the force, and 30 mM Mg^<2+> induced, myosin phosphorylation independent, force development, Also, blebbistatin accelerated relaxation by Ca^<2+> removal. IC_<50> values of the blebbistatin effects presented above were nearly 25 micro M. The present results suggested that blebbistain directly interfare cross-bridge interaction. Furthermore, blebbistatin inhibited organization of actin-and myosin-filaments. Since blebbistatin did not bind to actin directly, disruption of myosin filaments seemed to modulate actin filaments organization. Less

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (3 results)

All 2007 Other

All Journal Article (3 results)

  • [Journal Article] Mechanisms of the inhibitory effects of a phenoxazine compound, 2-amino-4, 4α-dihydro-4α-7-dimethyl-3H-phenoxazine-3-one on the contraction of smooth muscles in guinea pig taenia cecum.2007

    • Author(s)
      Musha S, Watanabe M, et al.
    • Journal Title

      Journal of Smooth Muscle Research 43・1(In Press)

    • NAID

      110006277704

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Mechanism of the inhibitory effects of a phenoxazine compound, 2-amino-4,1α-dihydro-4α-7-dimethyl-3H-phenoxazine-3-one on the contraction of smooth muscles in guinea pig taenia cecum.2007

    • Author(s)
      Musha S, Watanabe M, et al.
    • Journal Title

      Journal of Smooth Muscle Research 43・1(In Press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Mechanisms of the inhibitory effects of a phenoxazine compound, 2-amino-4, 4α-dihydro-4α-7-dimethy1-3H-phenoxazine-3-one on the contraction of smooth muscles in guinea pig taenia cecum.

    • Author(s)
      Saifuding Musha, Masaru Watanabe, Akio Tomoda, Masato Konishi.
    • Journal Title

      Jounral of Smooth Muscle Research (in Press)

      Pages: 34-1

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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