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

Treatment with acetylcholine (ACh) of a beta-escin-permeabilized intrapulmo nary bronchial smooth muscle of the rat induced force when the Ca2+ concent ration was clamped at 1 mu M. The ACh-induced Ca2+ sensitization of myofila ments was significantly greater in antigen-induced airway hyperresponsive r ats than in control rats. The ACh-induced Ca2+ sensitization was completely blocked by treatment with Clostridium botulinum C3 exoenzyme, an inactivat or of Rho family of proteins. Moreover, the protein level of RhoA in the in trapulmonary bronchi was significantly increased in the airway hyperrespons ive rats. Thus, increased airway smooth muscle contractility observed in as thmatics may be related to augmented agonist-induced, Rho-mediated Ca2+ sen sitization of myofilaments.