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GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Role of Adenosine A₁ Receptor in the Regulation of Gastrin Release

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

Adenosine has been demonstrated to inhibit gastric acid secretion. In the rat stomach, this inhibitory effect may be mediated indirectly by the inhibition of gastrin release. Results show that the A₁ receptor agonist N⁶-cyclopentyladenosine (CPA) suppressed immunoreactive gastrin (IRG) release in a concentration-dependent manner. CPA significantly inhibited IRG release at 0.001 µM and maximally inhibited IRG release at 1 µM. At concentrations of 0.001 to 0.1 µM, the A_2A receptor-selective agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine and A₃ receptor-selective agonist 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl--D-ribofuranuronamide, had no effect on IRG release, suggesting the involvement of A₁ receptors. In agreement, the A₁ receptor-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine abolished adenosine-induced inhibition of IRG release. Results of immunohistochemistry experiments reveal the presence of A₁ receptor immunoreactivity on mucosal G-cells and D-cells, and the gastric plexi, but not parietal cells, suggesting that adenosine may act directly on G-cells or indirectly on the gastric plexi to modulate IRG release. The structure of the mucosal A₁ receptor was found to be identical to that in the rat brain. Alternative splicing within the coding region of this receptor did not occur. A real-time reverse transcription-polymerase chain reaction assay was developed to measure gastric A₁ receptor gene expression. The highest level of gastric A₁ receptor mRNA was found in the corporeal muscle. However, this level was significantly lower in comparison with the striatum. In conclusion, this study shows that adenosine may suppress IRG release, at least in part, by activating A₁ receptors localized on G-cells and may consequently result in an inhibition of 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

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				L. Yip, H. C. H. Leung, and Y. N. Kwok Effect of Omeprazole on Gastric Adenosine A1 and A2A Receptor Gene Expression and Function J. Pharmacol. Exp. Ther., October 1, 2004; 311(1): 180 - 189. [Abstract] [Full Text] [PDF]