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

1 Transmurally stimulated segments of the guinea-pig ileum have been used to analyse the different adrenoceptors in the terminal (0 to 3 cm) and the proximal (> 50 cm from the ileocaecal valve) ileum.2 The prejunctional adrenoceptors (located on the final, cholinergic, motor nerve terminals) and postjunctional adrenoceptors (located on the smooth muscle membrane) have been characterized according to their sensitivity to alpha- and beta-agonists and antagonists.3 Phentolamine, phenoxybenzamine and yohimbine, in concentrations of 0.1 muM, transiently enhanced (up to 10%) the twitch response. At higher concentrations all the alpha- and beta-antagonists studied depressed the neurogenic twitches and relaxed the smooth muscle.4 The twitch-inhibitory effects of adrenoceptor agonists (noradrenaline, adrenaline and ephedrine) were not antagonized by phenoxybenzamine (0.1, 0.5 and 1 muM), carbidine (0.5, 1 and 5 muM) and propranolol (0.5, 1 and 5 muM); however, they were depressed by phentolamine (0.1, 0.5, 1.25 and 5 muM) and yohimbine (0.25, 0.5 and 5 muM).5 The smooth muscle contractions induced by noradrenaline and adrenaline in the terminal ileum and by phenylephrine in both the terminal and proximal ileum were antagonized by phenoxybenzamine, carbidine and phentolamine but were not influenced by yohimbine and propranolol.6 The smooth muscle relaxations of the proximal ileum induced by noradrenaline, adrenaline and ephedrine were inhibited by yohimbine, phentolamine, carbidine and phenoxybenzamine, and the isoprenaline-induced relaxation was antagonized by propranolol.7 All the agonists studied, except phenylephrine, elicited relaxations of the acetylcholine-induced sustained contraction of both proximal and terminal ileum. The relaxation induced by isoprenaline was antagonized by propranolol, and the effects of noradrenaline and ephedrine by yohimbine.8 It is concluded that in the guinea-pig ileum there are postsynaptic beta-adrenoceptors and at least two types of alpha-adrenoceptors: alpha(1)-excitatory postjunctional adrenoceptors activated by phenylephrine, noradrenaline and adrenaline and antagonized by phenoxybenzamine, carbidine and phentolamine; alpha(2)-inhibitory prejunctional adrenoceptors activated by ephedrine, noradrenaline and adrenaline and inhibited by yohimbine and phentolamine. The inhibitory postjunctional alpha-adrenoceptors are more close to the alpha(2)-adrenoceptors, since they were stimulated predominantly by ephedrine and noradrenaline and inhibited by yohimbine.9 It has been shown that all alpha-adrenoceptor subtypes are to be found at every distance (0 to 70 cm) from the ileocaecal valve and that they can be activated in the resting or in the acetylcholine-contracted states.