Mechanism of action of metoclopramide on opossum lower esophageal sphincter muscle.

The purpose of this study was to investigate the mechanism of action of metoclopramide on the lower esophageal sphincter (LES) muscle of the opossum. Metoclopramide gave a dose-related increase in LES muscle active tension. A peak response of 12.5 +/- 2.1 g (mean +/- SEM) was achieved at 3.1 X 10(-4) M. The maximal and submaximal LES muscle response to metoclopramide could not be antagonized by atropine, hyoscine, hexamethonium, tetrodotoxin, phentolamine, diphenhydramine, or propranolol. Metoclopramide did not augment the submaximal muscle responses to gastrin I, acetylcholine, or norepinephrine. These studies suggest that in the opossum, metoclopramide acts through a direct action on the smooth muscle.