Mechanism of the lower esophageal sphincter relaxation. Action of prostaglandin E 1 and theophylline

Abstract

The intravenous injection of prostaglandin E(1) (PGE(1)) causes a dose-dependent relaxation of the lower esophageal sphincter (LES) in the intact, lightly anesthetized opossum. The action of PGE(1) is not inhibited by the drugs that produce muscarinic or nicotinic cholinergic antagonism or alpha and beta adrenergic antagonism in the doses that inhibited the action of respective agonists. Moreover, this action is not affected by exogenous gastrin pentapeptide. The action of PGE(1) on the LES is mimicked by isoproterenol, theophylline ethylenediamine, and dibutyryl cyclic AMP. Both theophylline, a phosphodiesterase inhibitor, and isoproterenol, an adenyl cyclase stimulator, added to the action of PGE(1). On the other hand, adenyl cyclase inhibitor nicotinic acid, as well as phosphodiesterase stimulator, imidazole inhibited its action. Further, both nicotinic acid and imidazole inhibited the degree of LES relaxation produced by esophageal distension. These studies suggest that intracellular cyclic AMP may act as the "second messenger" in the regulation of the lower esophageal sphincter relaxation.