Adrenergic and VIP-ergic relaxatory mechanisms of the feline extrahepatic biliary tree.

Relaxatory mechanisms of the extrahepatic biliary tree were investigated in anesthetized cats allowing separate recordings of the sphincter of Oddi, gallbladder and duodenal wall. Regional intra-arterial administration of vasoactive intestinal peptide (VIP) elicited dose-dependent relaxatory motor responses, which were not influenced by blockade of cholino- or beta-adrenoceptors, but were most probably due to activation of VIP receptors at the smooth muscle membrane. Efferent electrical vagal nerve stimulation unmasked relaxatory motor responses after previous blockade of muscarinic cholinoceptors. The neural transmission did not involve beta-adrenoceptors but was effectively antagonized after additional blockade with hexamethonium. Since both nerve terminals and ganglion cells with VIP-like immunoreactivity were abundant in the feline sphincter of Oddi, VIP is one possible transmitter candidate of the postganglionic inhibitory neurons. Non-selective activation of beta-adrenoceptors by isoprenaline or selective activation of beta 2-adrenoceptors by terbutaline also induced a dose-dependent relaxation of these regions. On a molar basis, relaxation via beta-adrenoceptors was 40-50 times less potent than via VIP. Both types of beta-adrenergic relaxation were antagonized by propranolol. The terbutaline-induced responses were selectively antagonized by beta 2-adrenoceptor blockade. To evaluate the role of beta 1-adrenoceptors, non-selective stimulation with isoprenaline was given; this relaxation was little influenced by blockade of beta 2-adrenoceptors but was completely antagonized by propranolol. In all experiments using beta-adrenoceptor antagonists these drugs each increased the basal tone of the preparation suggesting release of tonic inhibition exerted via beta-adrenoceptors.