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

本研究旨在探讨rho激酶抑制剂Y-27632和法舒地尔对抗胆碱酯酶（anti-ChE）诱导的大鼠气管收缩反应和磷脂酰肌醇反应的影响。用大鼠气管环或气管片测定了体外等长张力和[^3H]肌醇单磷酸酯（IP_1）的形成。Y-27632和法舒地尔对新斯的明和吡啶斯的明诱导的收缩作用在30 μM时几乎完全抑制，而乙酰胆碱诱导的收缩作用在100 μM时分别被Y-27632和法舒地尔抑制56%和51%。法舒地尔对新斯的明和乙酰胆碱诱导的收缩的抑制作用被肌球蛋白磷酸酶抑制剂钙环素- a完全逆转。法舒地尔在100 μM下可减弱新斯的明诱导的IP1积累。结果表明，抗- ches部分通过激活rho激酶途径引起气道平滑肌收缩。

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.