Effect of omeprazole on gastric adenosine A1 and A2A receptor gene expression and function.
Adenosine has been shown to inhibit immunoreactive gastrin (IRG) release and to stimulate somatostatin-like immunoreactivity (SLI) release by activating adenosine A(1) and A(2A) receptors, respectively. Since the synthesis and release of gastrin and somatostatin are regulated by the acid secretory state of the stomach, the effect of achlorhydria on A(1) and A(2A) receptor gene expression and function was examined. Omeprazole-induced achlorhydria was shown to suppress A(1) and A(2A) receptor gene expression in the antrum and corporeal mucosa, but not in the corporeal muscle. Omeprazole treatment produced reciprocal changes in A(1) receptor and gastrin gene expression, and parallel changes in A(2A) receptor and somatostatin gene expression. The localization of A(1) and A(2A) receptors on gastrinsecreting G-cells and somatostatin-secreting D-cells, respectively, suggests that changes in adenosine receptor expression may modulate the synthesis and release of gastrin and somatostatin. Thus, the effect of omeprazole on adenosine receptor-mediated changes in IRG and SLI release was also examined in the vascularly perfused rat stomach. After omeprazole treatment, the A(1) receptor-mediated inhibition of IRG and SLI release induced by N(6)-cyclopentyladenosine (A(1) receptor-selective agonist) was not altered, but the A(2A) receptor-mediated augmentation of SLI release induced by 2-p-(2-carboxyethyl-)phenethylamino-5'-N-ethylcarboxamidoadenosine (A(2A)-selective agonist) was significantly attenuated. These findings agree well with the corresponding omeprazole-induced decrease in antral A(2A) receptor mRNA expression. Overall, the present study suggests that adenosine receptor gene expression and function may be altered by omeprazole treatment. Acid-dependent changes in adenosine receptor expression may represent a novel purinergic regulatory feedback mechanism in controlling gastric acid secretion.
Yip
Linda
L
Department of Physiology, University of British Columbia, 2146 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3.
Leung
Henry Chi Hang
HC
Kwok
Yin Nam
YN
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D005755:Gastrins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D010627:Phenethylamines / Q000494:pharmacology; D012337:RNA, Ribosomal, 18S / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000235:genetics / Q000378:metabolism*; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism*; D013004:Somatostatin / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D005755:Gastrins; D010627:Phenethylamines; D012337:RNA, Ribosomal, 18S; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C048599:N(6)-cyclopentyladenosine; D013004:Somatostatin; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D000241:Adenosine; D009853:Omeprazole