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

The effects of pharmacological stimulation at different levels of the beta-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 beta-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 mug/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 beta-AR agonists attenuate cholinergic neurotransmission in isolated bovine trachealis model by a mechanism not involving cAMP but K-Ca channels.