Gastrin-induced gene expression in oxyntic mucosa and ECL cells of rat stomach.
The histamine-producing ECL cells are numerous in the acid-producing (oxyntic) mucosa. They respond to gastrin by secretion of histamine that acts on parietal cells to produce acid. In addition, gastrin has a trophic effect on the oxyntic mucosa which is exerted on stem cells and ECL cells. To elucidate the molecular actions of gastrin on the stomach we attempted to identify genes that are regulated by gastrin in oxyntic mucosa and in isolated ECL cells. Differential display polymerase chain reaction was used to identify mRNAs that are differentially expressed in rats that are hypergastrinemic after treatment with the proton pump inhibitor omeprazole for 48 h compared with rats that are hypogastrinemic after 24 h fasting. Differences in mRNA levels were confirmed by Northern blot analysis (comparing mRNA from fasted rats, omeprazole-treated rats and rats treated with omeprazole + the CCK2 (cholecystokinin) receptor antagonist YF476). The cDNAs were identified by sequencing followed by data base search. Hypergastrinemia induced by omeprazole treatment resulted in overexpression of mRNA for histidine decarboxylase, fetuin, pepsinogen and cytochrome P450 in the oxyntic mucosa. This was prevented by CCK2 receptor blockade. In isolated ECL cells gastrin upregulated mRNAs for histidine decarboxylase and synaptotagmin V as well as one mRNA transcript without known homology.
Björkqvist
M
M
Department of Pharmacology, University of Lund, Sweden.
Lindström
E
E
Norlén
P
P
Groenborg
M
M
Håkanson
R
R
Gammeltoft
S
S
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005755:Gastrins / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D015347:RNA Probes; D051381:Rats; D017207:Rats, Sprague-Dawley
D017931:DNA Primers; D005755:Gastrins; D015347:RNA Probes