Mechanisms of the inhibitory action of prostaglandins on meal-induced gastric secretion.

Abstract

In dogs with gastric fistula and Heidenhain pouch (HP), 15(S)-15-methyl prostaglandin E2 methyl ester (PG-S) infused intravenously in graded doses (0.5--2.0 microgram/kg/h) inhibited dose-dependently, meal-induced acid secretion both from the vagally innervated main stomach and from the HP. This inhibition was associated with a marked reduction in mucosal blood flow but without significant change in the ratio of aminopyrine concentration in the gastric juice and blood plasma, indicating that the reduction in gastric microcirculation was probably secondary to the inhibition of gastric secretion. In dogs with special cannulae that allowed complete separation of the stomach and the intestine, PG-S caused stronger inhibition of gastric acid and serum gastrin responses to gastric and intestinal meals after application directly to the gastric mucosa, than following duodenal administration. PG-S applied topically to the HP mucosa also suppressed direct chemical stimulation of the HP by L-histidine meal. We conclude that PG-S exerts its inhibitory action on gastric secretion both by local contact with the mucosa via suppression on gastrin release from the antral G-cells and by direct inhibition of the secretory activity of the oxyntic glands.