Received for publication November 6, 2003.
Revised December 24, 2003.
Accepted for publication January 16, 2004.

Role of Adenosine A_2A Receptor in the Regulation of Gastric Somatostatin Release

Abstract

Adenosine has been demonstrated to inhibit gastric acid secretion. In the rat stomach, this inhibitory effect may be mediated indirectly by increasing the release of somatostatin-like immunoreactivity (SLI). Results show that adenosine analogs augmented SLI release in the isolated vascularly perfused rat stomach. The rank order of potency of the analogs in stimulating SLI release was 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) 5'-N-ethylcarboxamidoadenosine > 2-chloroadenosine > R(-)-N⁶-(2-phenylisopropyl)adenosine > 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl--D-ribofuranuronamide > N⁶-cyclopentyladenosine N⁶-cyclohexyladenosine > S(+)-N6-(2-phenylisopropyl)adenosine, suggesting the involvement of the A_2A receptor. In agreement, 4-(2-[7-Amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385), an A_2A receptor antagonist, was shown to abolish the adenosine- and CGS 21680-stiumlated SLI release. Immunohistochemical studies revealed the presence of A_2A receptor immunoreactivity (A_2AR-IR) on the gastric plexi and mucosal D-cells, but not on parietal cells and G-cells, suggesting that adenosine may act directly on D-cells or indirectly on the gastric plexi to augment SLI release. The present study also demonstrates that the structure of the mucosal A_2A receptor is identical to that in the rat brain, and that alternative splicing of this gene does not occur. A Real-Time RT-PCR assay has also been established to quantify the levels of A_2A receptor mRNA. Results show that gastric tissues contained significantly lower levels of A_2A receptor mRNA compared to the striatum. The lowest level was detected in the mucosa. In conclusion, adenosine may act on A_2A receptors to augment SLI release and consequently control gastric acid secretion.

Key words: Adenosine, CGS 21680, Real-Time RT-PCR, gastric acid, gastrin, somatostatin

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