Control of gastric acid secretion: the gastrin-ECL cell-parietal cell axis

Gastric acid secretion is under nervous and hormonal control. Gastrin, the major circulating stimulus of acid secretion, probably does not stimulate t he parietal cells directly but acts to mobilize histamine from the ECL cell s in the oxyntic mucosa. Histamine stimulates the parietal cells to secrete HCl. The gastrin-ECL cell pathway has been investigated extensively in sit u (gastric submucosal microdialysis), in vitro (isolated ECL cells) and in vivo (intact animals). Gastrin acts on CCK, receptors to control the synthe sis of ECL-cell histamine, accelerating the expression of the histamine-for ming enzyme histidine decarboxylase (HDC) at both the transcription and the translation/posttranslation levels. Depletion of histamine by alpha -fluor omethylhistidine (an irreversible inhibitor of HDC) prevents gastrin-induce d but not histamine-induced gastric acid secretion. Acute CCK, receptor blo ckade inhibits gastrin-evoked but not histamine-induced acid secretion. Stu dies both in vivo/in situ and in vitro have suggested that while acetylchol ine seems capable of activating parietal cells, it does not affect histamin e secretion from ECL cells. Unlike acetylcholine, the neuropeptides pituita ry adenylate cyclase-activating peptide and vasoactive intestinal peptide m obilize ECL-cell histamine. Whether vagally stimulated acid secretion refle cts an effect of the enteric nervous system on the ECL cells (neuropeptides ) and/or a direct one on the parietal cells needs to be further investigate d. (C) 2001 Elsevier Science Inc. All rights reserved.