INHIBITION OF RABBIT DUODENAL BICARBONATE SECRETION BY ULCEROGENIC AGENTS - HISTAMINE-DEPENDENT AND HISTAMINE-INDEPENDENT EFFECTS

Background & Aims: The gastroduodenal epithelium is protected from aci d-peptic damage, in part, by its ability to secrete bicarbonate. Patie nts with duodenal ulcer disease have impaired proximal duodenal mucosa l bicarbonate secretion. We have shown in vitro that histamine inhibit s prostaglandin-stimulated bicarbonate secretion in rabbit duodenal mu cosa via histamine H-2 receptors and enteric nerves. In this study we examined whether the proulcerogenic compounds aspirin or ethanol regul ate duodenal bicarbonate secretion and the involvement of histamine. M ethods: Bicarbonate secretion by rabbit proximal duodenal mucosa was e xamined in vitro in Ussing chambers. Results: Aspirin and ethanol decr eased basal and prostaglandin-stimulated bicarbonate secretion; the la tter effect was specific for prostaglandin. The inhibitory effects of the two ulcerogenic compounds were at least additive. Ranitidine and t etrodotoxin abolished the inhibitory effects on stimulated, but not ba sal, secretion. Aspirin and ethanol also induced release of duodenal h istamine. Conclusions: Aspirin and ethanol act by two distinct pathway s to impair duodenal bicarbonate secretion. Both agents inhibit basal secretion via a histamine-independent and neurally independent pathway while they inhibit prostaglandin E-2-stimulated secretion via histami ne release, likely from mast cells, and actions on enteric nerves. Our findings may be of relevance to the understanding and potential treat ment of nonsteroidal anti-inflammatory drug-associated mucosal injury.