Effects of leukotriene D4, the antagonist L-649-923, and arachidonic acid on duodenal bicarbonate secretion in the rat in vivo.

Prostaglandins of the E type stimulate bicarbonate secretion by the duodenal mucosa and inhibit gastric acid secretion, effects that have been related to their anti-ulcer activity. Leukotrienes constitute a more recently discovered branch of the arachidonic acid cascade, and C4 and D4 have been suggested to be ulcerogenic in the stomach. We have studied the effects of luminal administration of leukotriene D4 and the leukotriene C4/D4 antagonist L-649-923 on duodenal mucosal alkaline secretion in the anaesthetized rat. Leukotriene D4 (10(-8)-10(-6) M) had no significant effects, but the antagonist dose-dependently increased the bicarbonate secretion and also transiently increased the transmucosal electric potential difference. The precursor arachidonic acid (10(-7)-10(-6) M) caused a small increase in secretion. The increase in bicarbonate secretion in response to 10(-3) M of the antagonist was of about the same magnitude as that observed with 10(-5) of prostaglandin E2, and it was abolished by pretreatment with the cyclooxygenase inhibitor indomethacin. The gastroduodenal protective effects of L-649-923 in vivo may reflect an increase in mucosal prostaglandin production rather than leukotriene antagonism.