Distribution and types of adrenoceptors in the guinea-pig ileum: the action of alpha- and beta-adrenoceptor agonists.

1 Segments of guinea-pig ileum and the myenteric plexus-longitudinal smooth muscle preparation were used for a study of the actions of adrenaline, noradrenaline, isoprenaline, ephedrine and phenylephrine on the responses of coaxially stimulated ileum at different distances from the ileocaecal valve.2 The responses of the ileum to electrical stimulation were suppressed by adrenaline, nonadrenaline and ephedrine, while phenylephrine and isoprenaline inhibited them only partially.3 The twitch inhibition elicited by these adrenoceptor agonists was the same at all distances from the ileocaecal valve. There was no significant difference between their cumulative and non-cumulative concentration-response curves.4 Smooth muscle relaxation was induced only by isoprenaline and contraction only by phenylephrine at all distances from the ileocaecal junction. Adrenaline and noradrenaline evoked smooth muscle contraction in the terminal (0 to 20 cm), a concentration-dependent, biphasic response in the intermediate part (21 to 50 cm) and a relaxation in the proximal ileum (> 50 cm from the ilecocaecal valve). Ephedrine did not change significantly the smooth muscle tension in the terminal and the intermediate segments and induced smooth muscle relaxation in the proximal ones.5 Ouabain and a potassium-free solution did not appear to influence the prejunctional action of noradrenaline nor the amplitude of smooth muscle relaxation in the proximal ileum, whereas the concentration-contractor response curves were significantly depressed and shifted to the right by ouabain and in a potassium-free solution.6 The brief initial (phasic) contraction induced by acetylcholine was not influenced during the sustained increase or decrease in tension induced by catecholamines. On the contrary, the stimulatory catecholamine actions disappeared or were changed to smooth muscle relaxation by acetylcholine pretreatment. Potassium chloride pretreatment did not change the character of the adrenoceptor agonist action of the agonists studied.7 Since there is a similar prejunctional action at all distances from the ileocaecal valve and a different postjunctional effect of the adrenoceptor agonists at different distances from the ileocaecal junction, it could be suggested that in the guinea-pig ileum there are at least two alpha-adrenoceptors (inhibitory prejunctional-alpha(2), stimulatory postjunctional-alpha(1)), an inhibitory postjunctional beta-adrenoceptor and an as yet uncharacterized inhibitory postjunctional receptor.8 Based on the specific postjunctional action of phenylephrine and the prejunctional action of ephedrine in the guinea-pig ileum, these drugs could be used with success as ;specific' alpha(1)- and alpha(2)-adrenoceptor stimulants.