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Modulation of cholinergic responsiveness through the -adrenoceptor signal transmission pathway in bovine trachealis

Servizio di Fisiopatologia Respiratoria, Dipartimento di Medicina Interna e Specialità Mediche, Università di Genova, 16132 Genova, Italy

Submitted 13 January 2003 ; accepted in final form 23 April 2003

The effects of pharmacological stimulation at different levels of the -adrenoceptor (AR) pathway, including the receptor, the receptor-coupled G_s protein, and adenylyl cyclase, were studied by simultaneous measurements of acetylcholine (ACh) release and isometric force evoked by electric stimulation in isolated bovine trachealis. The -AR agonists isoproterenol (10^-6 and 10^-5 M) and salbutamol (10^-7 to 10^-5 M) significantly attenuated both ACh release and contractile force. Forskolin, at 10^-6 M, significantly increased ACh release without effect on contractile force, whereas at 10^-5 M it increased ACh release but significantly decreased force. Activation of G_s protein by cholera toxin (10 µg/ml) significantly attenuated both ACh release and contractile force, but its effect on ACh release was abolished by calcium-activated potassium (K_Ca)-channel blocker iberiotoxin (10^-7 M). The K_Ca-channel opener NS-1619 (10^-4 M) attenuated significantly both ACh release and contractile force. It is concluded that -AR agonists attenuate cholinergic neurotransmission in isolated bovine trachealis model by a mechanism not involving cAMP but K_Ca channels.

acetylcholine release; airway smooth muscle; G_s protein; cAMP; calcium-activated potassium channels

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