Histamine inhibits prostaglandin E 2-stimulated rabbit duodenal bicarbonate secretion via H 2 receptors and enteric nerves

Abstract

Background/Aims: The gastroduodenal epithelium is protected from acid peptic damage by an adherent mucus-bicarbonate layer. Bicarbonate is secreted by the surface epithelial cells into this mucus layer. Patients with duodenal ulcer disease have impaired proximal duodenal bicarbonate secretion. Mast cells, present in large numbers in the duodenal mucosa, release a number of inflammatory mediators, including histamine. Release of such mast cell mediators has been implicated in ulcer disease. In this study, the ability of histamine to regulate bicarbonate secretion was examined. Methods: Bicarbonate secretion by rabbit proximal duodenal mucosa was examined in vitro, and the effects of histamine, its agonists, and its antagonists were studied. Results: Histamine essentially eliminated prostaglandin E 2-stimulated duodenal mucosal bicarbonate secretion, an effect reversed both by the neurotoxin, tetrodotoxin, and the histamine H 2-receptor antagonist, cimetidine, as well as reproduced by the H 2-receptor agonist, dimaprit. Conclusions: In addition to the stimulatory action of histamine on gastric acid secretion, histamine expresses an additional antidefensive action by inhibiting prostaglandin E 2-stimulated duodenal epithelial bicarbonate secretion. This effect of histamine is likely mediated via H 2 receptors located on enteric nerves.