Anesth Analg 2006;102:1121-1126
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ane.0000198584.26710.68
ANESTHETIC PHARMACOLOGY
Anticholinesterase Drugs Stimulate Smooth Muscle Contraction of the Rat Trachea Through the Rho-Kinase Pathway
Osamu Shibata, MD,
Masataka Saito, MD,
Maki Yoshimura, MD,
Masakazu Yamaguchi, MD,
Kenji Nishioka, MD,
Tetsuji Makita, MD, and
Koji Sumikawa, MD
Department of Anesthesiology, Nagasaki University School of Medicine, Nagasaki, Japan
Address correspondence and reprint requests to Osamu Shibata, MD, Department of Anesthesiology, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. Address e-mail to opshiba{at}net.nagasaki-u.ac.jp.
We 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 µM each, whereas 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.
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