Possible involvement of G(i3) protein in augmented contraction of bronchial smooth muscle from antigen-induced airway hyperresponsive rats.
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 microg/mL for 6 hr, 37 degrees ), whereas only a slight attenuation was observed in the normal control group. The level of G(alpha)i3 (measured by immunoblotting), but not other alpha-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 G(alpha)i3 protein of bronchial smooth muscle.
Department of Pharmacology, Hoshi University, School of Pharmacy, 2-4-41 Ebara, Shinagawa-ku, 142-8501, Tokyo, Japan. chiba@hoshi.ac.jp
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Chiba
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Sakai
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Misawa
D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D016535:Bronchial Hyperreactivity / Q000378:metabolism / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D037342:Pertussis Toxin; D051381:Rats; D017208:Rats, Wistar; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000109:Acetylcholine