Inhibition of rabbit intestine mediated by alpha- and beta-adrenoceptors

1. The effects of some alpha- and beta-adrenoceptor agonists and antagonists were studied on isolated segments of rabbit intestine in an attempt to characterize the two types of inhibitory response produced by sympathomimetic amines.2. Phenylephrine, an alpha-adrenoceptor agonist, produced an inhibition of rapid onset, from which recovery occurred despite the continued presence of the drug. On washout there was an overshoot in contraction height. Isoprenaline, a beta-adrenoceptor agonist, produced an inhibition of slow onset which was maintained throughout the presence of the drug and there was no overshoot on washout.3. Adrenaline resembled phenylephrine more closely than it resembled isoprenaline, in that it showed more affinity for alpha-adrenoceptors, whereas noradrenaline, and the transmitter released on periarterial nerve stimulation, behaved more like isoprenaline, although both types of receptor were affected.4. Adenosine-5'-triphosphate produced an inhibition resembling that produced by an alpha-adrenoceptor agonist, whereas the dibutyryl analogue of cyclic adenosine 3',5'-monophosphate (cyclic 3',5'-AMP) produced an inhibition resembling that produced by a beta-adrenoceptor agonist.5. In critical concentrations theophylline augmented and imidazole inhibited beta-adrenoceptor mediated responses, as well as responses to dibutyryl cyclic AMP. However, additional actions of theophylline and imidazole were also demonstrated.6. Responses mediated by alpha-adrenoceptors, but not those mediated by beta-adrenoceptors, were blocked by membrane stabilizers, quinidine being the most potent of those studied.7. The results are discussed in relation to the possible mechanisms of action of alpha- and beta-adrenoceptor agonists.