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Mechanisms of airway smooth muscle contraction : physio-pharmacologic factors and intracellular signaling pathway

Research Project

Project/Area Number 15591638
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionNagasaki University Hospital of Medicine and Dentistry

Principal Investigator

SHIBATA Osamu  Nagasaki University Hospital of Medicine and Dentistry, Anesthesiology, Associate Professor, 医学部・歯学部附属病院, 助教授 (80136671)

Co-Investigator(Kenkyū-buntansha) MAKITA Tetsuji  Nagasaki University Hospital of Medicine and Dentistry, Anesthesiology, Instructor, 医学部・歯学部附属病院, 講師 (00229337)
YAMAGUCHI Masakazu  Nagasaki University Hospital of Medicine and Dentistry, Anesthesiology, Assistant Professor, 医学部・歯学部附属病院, 助手 (80363498)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsAnticholinesterases / Rho-kinase / Phosphatidylinositol / Muscarinic M3 receptor / Rat / 抗コリンエステラーゼ / Y-27632
Research Abstract

This study was carried out to determine the effects of Rho-kinase inhibitors, Y-27632 and fasudil, on the anticholinesterase (anti-ChE)-induced contractile and phosphatidylinositol responses of rat trachea. In vitro measurements of isometric tension and [^3H] inositol monophosphate (IP_1) formed were conducted by using rat tracheal rings or slices. Neostigmine- and pyridostigmine-induced contractions were almost completely inhibited by Y-27632 and fasudil at 30 μM for each, while acetylcholine-induced contraction was inhibited incompletely, i.e., by 56% by Y-27632 and by 51% by fasudil, at 100 μM for each, respectively. The inhibitory effects of fasudil on neostigmine- and acetylcholine-induced contractions were completely reversed by calyculin-A, a myosin phosphatase inhibitor. Neostigmine-induced IP1 accumulation was attenuated by fasudil at 100 μM. The results suggest that anti-ChEs cause airway smooth muscle contraction in part through activation of the Rho-kinase pathway.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (10 results)

All 2006 2004 Other

All Journal Article (7 results) Publications (3 results)

  • [Journal Article] Propofol attenuates ovalbumin-induced smooth muscle contraction of the sensitized rat trachea; inhibition of serotonergic and cholinergic signaling.2006

    • Author(s)
      Yamaguchi M, Shibata O, Nishioka K, Makita T, Sumikawa K.
    • Journal Title

      Anesth Analg. (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Anticholinesterase drugs stimulate smooth muscle contraction of the rat trachea through the Rho-kinase pathway.2006

    • Author(s)
      Shibata O, Saito M, Yoshimura M, Yamaguchi M, Nishioka K, Makita T, Sumikawa K.
    • Journal Title

      Anesth Analg. 102

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Anticholine sterase dmgs stimulate smooth muscle contraction of the rat trachea through the Rho-kinase pathway2006

    • Author(s)
      Shibata O
    • Journal Title

      Anesth Analg (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Selegiline, an MAO-B inhibitor, attenuates airway smooth muscle contraction in the rat trachea2004

    • Author(s)
      Yoshimura M, Shibata O, Saito M, Yamaguchi M, Nishioka K, Makita T, Sumikawa K.
    • Journal Title

      J Pharm Pharmacol. 56

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Metoclopramide causes airway smooth muscle relaxation through inhibition of muscarinic M3 receptor in the rat trachea.2004

    • Author(s)
      Saito M, Shibata O, Yamaguchi M, Yoshimura M, Makita T, Niwa M, Sumikawa K.
    • Journal Title

      Anesth Analg. 98

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Selegiline, an MAO-B inhibitor, attenuates airway smooth muscle contraction in the rat trachea.2004

    • Author(s)
      Yoshimura M
    • Journal Title

      J Pharm Pharmacol 56

      Pages: 935-939

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Metoclopramide causes airway smooth muscle relaxation through inhibition of muscarinic M3 receptor in the rat trachea.2004

    • Author(s)
      Saito M
    • Journal Title

      Anesth Analg 98

      Pages: 1325-1329

    • Related Report
      2004 Annual Research Report
  • [Publications] Saito M: "Metoclopramide causes airway smooth muscle relaxation through inhibition of muscarinic M_3 receptor in the rat"Anesth Analg. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shibata O: "Interactions of edrophonium with neostigmine in the rat trachea"Anesth Analg. 97・4. 1059-1063 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shibata O: "Droperidol attenuates contratile and phosphatidyl-inositol responses of rat trachea"Pharmacology. 68・1. 24-28 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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