Gastrin-induced gene expression in oxyntic mucosa and ECL cells of rat stomach

The histamine-producing ECL cells are numerous in the acid-producing (oxynt ic) mucosa. They respond to gastrin by secretion of histamine that acts on parietal cells to produce acid. In addition, gastrin has a trophic effect o n the oxyntic mucosa which is exerted on stem cells and ECL cells. To eluci date the molecular actions of gastrin on the stomach we attempted to identi fy genes that are regulated by gastrin in oxyntic mucosa and in isolated EC L cells. Differential display polymerase chain reaction was used to identif y mRNAs that are differentially expressed in rats that are hypergastrinemic after treatment with the proton pump inhibitor omeprazole for 48 h compare d with rats that are hypogastrinemic after 24 h fasting. Differences in mRN A levels were confirmed by Northern blot analysis (comparing mRNA from fast ed rats, omeprazole-treated rats and rats treated with omeprazole + the CCK , (cholecystokinin) receptor antagonist YF476). The cDNAs were identified b y sequencing followed by data base search. Hypergastrinemia induced by omep razole treatment resulted in overexpression of mRNA for histidine decarboxy lase, fetuin, pepsinogen and cytochrome P450 in the oxyntic mucosa. This wa s prevented by CCK2 receptor blockade. In isolated ECL cells gastrin upregu lated mRNAs for histidine decarboxylase and synaptotagmin V as well as one mRNA transcript without known homology. (C) 1999 Elsevier Science B.V. All rights reserved.