Possible involvement of G i3 protein in augmented contraction of bronchial smooth muscle from antigen-induced airway hyperresponsive rats

Abstract

To investigate a possible involvement of pertussis toxin (PTX)-sensitive heterotrimeric G proteins in the pathogenesis of airway hyperresponsiveness, the effect of PTX treatment on the augmented contractile response to acetylcholine (ACh) in bronchial smooth muscle of antigen-induced airway hyperresponsive rats was determined. In bronchial smooth muscle of airway hyperresponsive rats that were actively sensitized and repeatedly challenged with 2,4-dinitrophenylated Ascaris suum antigen, ACh-induced contractions were markedly augmented. The augmented contractile responses in the airway hyperresponsive group were significantly inhibited after treatment with PTX (1 μg/mL for 6 hr, 37°), whereas only a slight attenuation was observed in the normal control group. The level of Gα i3 (measured by immunoblotting), but not other α-subunits of G i/o family proteins, in bronchial smooth muscle of the airway hyperresponsive rats was significantly increased as compared with that of control animals. It is concluded that PTX-sensitive muscarinic contractile responses of bronchial smooth muscle might be augmented upon antigen-induced airway hyperresponsiveness in rats, probably due to an up-regulation of Gα i3 protein of bronchial smooth muscle.