Role of adenosine A1 receptor in the regulation of gastrin release.
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 A(1) receptor agonist N(6)-cyclopentyladenosine (CPA) suppressed immunoreactive gastrin (IRG) release in a concentration-dependent manner. CPA significantly inhibited IRG release at 0.001 microM and maximally inhibited IRG release at 1 microM. At concentrations of 0.001 to 0.1 microM, the A(2A) receptor-selective agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine and A(3) receptor-selective agonist 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-beta-d-ribofuranuronamide, had no effect on IRG release, suggesting the involvement of A(1) receptors. In agreement, the A(1) receptor-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine abolished adenosine-induced inhibition of IRG release. Results of immunohistochemistry experiments reveal the presence of A(1) 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 A(1) 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 A(1) receptor gene expression. The highest level of gastric A(1) 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 A(1) receptors localized on G-cells and may consequently result in an inhibition of 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; D058907:Adenosine A1 Receptor Agonists; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism*; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000502:physiology*
D058907:Adenosine A1 Receptor Agonists; D005755:Gastrins; D010627:Phenethylamines; D043682:Receptor, Adenosine A1; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000241:Adenosine