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GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Effect of Omeprazole on Gastric Adenosine A₁ and A_2A Receptor Gene Expression and Function

Department of Physiology, University of British Columbia, Vancouver, British Columbia, Canada

Adenosine has been shown to inhibit immunoreactive gastrin (IRG) release and to stimulate somatostatin-like immunoreactivity (SLI) release by activating adenosine A₁ 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 A₁ and A_2A receptor gene expression and function was examined. Omeprazole-induced achlorhydria was shown to suppress A₁ and A_2A receptor gene expression in the antrum and corporeal mucosa, but not in the corporeal muscle. Omeprazole treatment produced reciprocal changes in A₁ receptor and gastrin gene expression, and parallel changes in A_2A receptor and somatostatin gene expression. The localization of A₁ 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 A₁ receptor-mediated inhibition of IRG and SLI release induced by N⁶-cyclopentyladenosine (A₁ 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.

Address correspondence to: Dr. Yin Nam Kwok, Department of Physiology, University of British Columbia, 2146 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3. E-mail: kynkwok{at}interchange.ubc.ca