Pharmacological characterization of the adrenoceptors in the muscularis mucosae of the guinea-pig esophagus

Abstract

Pharmacological characteristics of the post-junctional adrenoceptors in the muscularis mucosae of the guinea-pig esophagus were examined in vitro. In the presence of propranolol (3 μM), all catecholamines, phenylephrine and methoxamine produced a weak contraction of the isolated muscularis mucosae. The order of potency of the contractile response was adrenaline > noradrenaline > methoxamine > phenylephrine and much weaker isoproterenol, dopamine and clonidine. The contractile responses to noradrenaline (10 μM) and adrenaline (10 μM) were markedly inhibited by phentolamine (3 μM), prazosin (3 μM), indomethacin (1 μM), aspirin (100 μM) and polyphloretin phosphate (30 μg/ml), and slightly by yohimbine (3 μM). On the other hand, all catecholamines and terbutaline produced relaxation of the isolated muscularis mucosae which was maximally contracted with carbachol (3 μM) in the presence of phentolamine (10 μM), in a concentrationdependent manner. The order of potency of the inhibitory response was isoproterenol > noradrenaline > adrenaline and much weaker terbutaline and dopamine. The inhibitory responses to catecholamines were competitively antagonized by three β blockers, being in the following order of potency as estimated by their pA₂ values: propranolol > atenolol ?? butoxamine. The pretreatment of the tissue with indomethacin (1 μM) did not modify the inhibitory responses to catecholamines. These results suggest that the guinea-pig esophageal muscularis mucosae has excitatory α₁ adrenoceptors and inhibitory β₁ adrenoceptors, and the α₁, but not β₁, adrenoceptors may link with the endogenous arachidonic acid cascade.