Change in RhoA activating mechanism in airway hyperresponsive bronchial smooth muscle.

1.正常大鼠经ACh收缩后，一种单体GTP结合蛋白RhoA移位到质膜上(RhoA活化)。反复抗原攻击的大鼠的支气管肌被ACh更明显地收缩，肌肉中的RhoA活性也更显著地增强。这些结果提示，RhoA活性增强可能是过敏性哮喘患者气道高反应性的重要因素。在β-七叶皂苷钠稳定的肺内支气管平滑肌上，ACh在相同的[Ca^&lt；2+&gt；]_i下引起进一步收缩，即Ca^&lt；2+&gt；敏化。Rho激酶(ROCK)抑制剂Y-27632可完全阻断RhoA/ROCK介导的Ca~(2+)敏化，提示RhoA/ROCK介导的Ca~(2+)敏化可能参与了气道高反应性。ACh对抗原攻击的支气管平滑肌的收缩作用明显增强，而对气管平滑肌的收缩作用不明显。这与这样一个事实相关联，即在抗原处理的大鼠中，RhoA在支气管而不是气管的平滑肌中的表达显著增加。提示RhoA的高表达在支气管平滑肌高反应性的形成中起重要作用。

1. When bronchial smooth muscle contracted by ACh in normal rats, a monomeric GTP binding protein, RhoA, translocated to plasma membrane (RhoA activation). The bronchial muscle from repeatedly antigen-challenged rats more markedly contracted by ACh, and the RhoA activation was also more markedly augmented in the muscle. These suggest that augmentation of RhoA activation may be a crucial factor in airway hyperresponsiveness at allergic bronchial asthma.2. In β-escin-penneabilized intrapulmonary bronchial smooth muscle, ACh induced a further contraction under the same [Ca^<2+>]_i, i.e. Ca^<2+> sensitization. Rho kinase (ROCK) inhibitor, Y-27632, completely blocked the Ca^<2+> sensitization, suggesting that RhoA/ROCK-mediated Ca^<2+> sensitization may be involved in the airway hyperesponsiveness.3. An augmentation of ACh-induced contraction of antigen-challenged bronchial smooth muscle was obviously observed, but that of tracheal smooth muscle was not. This correlated the fact that RhoA expression in bronchial, but not tracheal, smooth muscle was significantly increased in the antigen-treated rats. This suggests that the increased expression of RhoA has an important role in developing hyperesponsiveness of bronchial smooth muscle.