Anticholinesterase drugs stimulate smooth muscle contraction of the rat trachea through the Rho-kinase pathway

Autor: Tetsuji Makita, Koji Sumikawa, Kenji Nishioka, Osamu Shibata, Maki Yoshimura, Masakazu Yamaguchi, Masataka Saito
Rok vydání: 2006
Předmět:
Zdroj: Anesthesia and analgesia. 102(4)
ISSN: 1526-7598
Popis: 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 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.
Databáze: OpenAIRE