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

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 15591638
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Nagasaki 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
• Keywords: Anticholinesterases / Rho-kinase / Phosphatidylinositol / Muscarinic M3 receptor / Rat

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.

Research Products

• [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
• [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 Pages: 1121-6.
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Selegiline, an MAO-B inhibitor, attenuates airway smooth muscle contraction in the rat trachea (2004)
  • Author(s): Yoshimura M, Shibata O, Saito M, Yamaguchi M, Nishioka K, Makita T, Sumikawa K.
  • Journal Title: J Pharm Pharmacol. 56 Pages: 935-9.
  • Description: 「研究成果報告書概要(和文)」より
• [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 Pages: 1325-9.
  • Description: 「研究成果報告書概要(和文)」より