[Probable involvement of the augmented agonist-induced Ca2+ sensitization of airway smooth muscle contraction in the pathogenesis of airway hyperresponsiveness].
Nonspecific airway hyperresponsiveness (AHR) is a common feature of allergic bronchial asthmatics, but the underlying mechanism (s) of AHR have yet to be elucidated. The importance of AHR in the pathogenesis of asthma has been suggested by its relevance to the severity of this disease. There is thus a need to understand the underlying mechanisms of AHR for the sake of asthma therapy. In the present minireview, we discussed the involvement of the augmented agonist-induced Ca2+ sensitization of airway smooth muscle contraction in the pathogenesis of AHR. Treatment with acetylcholine (ACh) of a beta-escin-permeabilized intrapulmonary bronchial smooth muscle of the rat induced a stronger contractile force even when the Ca2+ concentration was clamped at 1 microM. The ACh-induced Ca2+ sensitization of myofilaments was found to be 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 the Rho family proteins. Moreover, the protein level of RhoA in the intrapulmonary bronchi was demonstrated to be significantly increased in the airway hyperresponsive rats. Thus, the increased airway smooth muscle contractility observed in asthmatics may be related to the augmented agonist-induced, Rho-mediated Ca2+ sensitization of myofilaments.
Chiba
Y
Y
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Misawa
M
M
D000109:Acetylcholine / Q000494:pharmacology*; D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000378:metabolism*; D051381:Rats; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D020742:rhoA GTP-Binding Protein; D000109:Acetylcholine; D002118:Calcium