Alpha- and beta-adrenoceptor-mediated responses of the guinea-pig ileum and the effects of neuronal uptake inhibition

Abstract

The effects of noradrenaline and isoprenaline were examined on preparations of guinea-pig ileum, in which contractions were induced by three different methods; by transmural electrical stimulation, by exogenous carbachol and by potassium depolarization. Alpha- or beta-adrenoceptor-mediated responses were examined by construction of cumulative concentration-response curves in the presence of propranolol (10(-6) M) and phentolamine (5 X 10(-6) M) respectively. Stimulation of alpha-adrenoceptors by noradrenaline virtually abolished the twitches from transmural stimulation, but only partially inhibited the carbachol- and potassium-induced contractions. The effects on the last two preparations were attributed to a post-synaptic inhibition at alpha-adrenoceptors on the longitudinal smooth muscle. In the transmurally-stimulated preparation there was an additional pre-synaptic alpha-adrenoceptor-mediated inhibition of cholinergic transmission. The maximum beta-adrenoceptor-mediated inhibition of all three preparations to noradrenaline and isoprenaline was of the same magnitude and attributed only to a post-synaptic action on longitudinal smooth muscle. The predominant post-synaptic beta-adrenoceptor-mediated (carbachol-contracted ileum) and pre-synaptic alpha-adrenoceptor-mediated (transmurally-stimulated ileum) relaxations were significantly (P less than 0.05) potentiated by the neuronal uptake inhibitor desmethylimipramine. These receptors may therefore be considered to be closely associated with the sympathetic innervation. The effect on the post-synaptic alpha-adrenoceptor-mediated relaxation was equivocal. Additional minor excitatory responses were identified as a direct alpha-adrenoceptor-mediated contractile response to noradrenaline and as a beta-adrenoceptor-mediated potentiation of transmural stimulation by isoprenaline, possibly due to facilitation of cholinergic transmitter release.