• Osamu Shibata, Masataka Saito, Maki Yoshimura, Masakazu Yamaguchi, Kenji Nishioka, Tetsuji Makita, and Koji Sumikawa.
• Department of Anesthesiology, Nagasaki University School of Medicine, Nagasaki, Japan. opshiba@net.nagasaki-u.ac.jp
• Anesth. Analg. 2006 Apr 1; 102 (4): 1121-6.

AbstractWe performed this study to determine the effects of Rho-kinase inhibitors, Y-27632 and fasudil, on the anticholinesterase (anti-ChE)-induced contractile and phosphatidylinositol responses of the rat trachea. In vitro measurements of isometric tension and [3H] inositol monophosphate (IP1) that was 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 microM each, whereas acetylcholine-induced contraction was inhibited incompletely, i.e., by 56% by Y-27632 and by 51% by fasudil, at 100 microM 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 microM. The results suggest that anti-ChEs cause airway smooth muscle contraction, in part, through activation of the Rho-kinase pathway.

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