Augmented acetylcholine-induced, Rho-mediated Ca(2+) sensitization of bronchial smooth muscle contraction in antigen-induced airway hyperresponsive rats

Treatment with acetylcholine (ACh) of a β-escin-permeabilized intrapulmonary bronchial smooth muscle of the rat induced force when the Ca(2+) concentration was clamped at 1 μM. The ACh-induced Ca(2+) sensitization of myofilaments was significantly greater in antigen-induced airway hyperresponsive rats than in control rats. The ACh-induced Ca(2+) 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 Ca(2+) sensitization of myofilaments