Effects of Leukotriene D₄, the Antagonist L-649-923, and Arachidonic Acid on Duodenal Bicarbonate Secretion in the Rat in Vivo

Abstract

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.

Key Words:

• Arachidonic acid
• bicarbonate secretion
• duodenal mucosa
• leukotriene D₄
• mucosal protection
• prostaglandin E₂