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在抗原诱导的气道高反应性大鼠中,乙酰胆碱诱导的支气管平滑肌收缩增强,Rho介导的Ca2+敏感性增强

Augmented acetylcholine-induced, Rho-mediated Ca2+ sensitization of bronchial smooth muscle contraction in antigen-induced airway hyperresponsive rats.

作者信息

Chiba Y, Takada Y, Miyamoto S, MitsuiSaito M, Karaki H, Misawa M

机构信息

Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.

出版信息

Br J Pharmacol. 1999 Jun;127(3):597-600. doi: 10.1038/sj.bjp.0702585.

Abstract

Treatment with acetylcholine (ACh) of a beta-escin-permeabilized intrapulmonary bronchial smooth muscle of the rat induced force when the Ca2+ concentration was clamped at 1 microM. The ACh-induced Ca2+ sensitization of myofilaments was significantly greater in antigen-induced airway hyperresponsive rats than in control rats. The ACh-induced Ca2+ sensitization was completely blocked by treatment with Clostridium botulinum C3 exoenzyme, an inactivator of Rho family of proteins. Moreover, the protein level of RhoA in the intrapulmonary bronchi was significantly increased in the airway hyperresponsive rats. Thus, increased airway smooth muscle contractility observed in asthmatics may be related to augmented agonist-induced, Rho-mediated Ca2+ sensitization of myofilaments.

摘要

当将大鼠肺内支气管平滑肌用β-七叶皂苷通透化处理,并将Ca2+浓度钳制在1微摩尔时,用乙酰胆碱(ACh)处理可诱导产生张力。抗原诱导的气道高反应性大鼠中,ACh诱导的肌丝Ca2+敏感性显著高于对照大鼠。用肉毒杆菌C3外毒素(一种Rho家族蛋白的失活剂)处理可完全阻断ACh诱导的Ca2+敏感性。此外,气道高反应性大鼠肺内支气管中RhoA的蛋白水平显著升高。因此,哮喘患者中观察到的气道平滑肌收缩性增加可能与激动剂诱导的、Rho介导的肌丝Ca2+敏感性增强有关。

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