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Adenosine A₁ and A₂₄ receptors in the rat stomach : biological actions, cellular localization, structure and gene expression Yip, Linda

Abstract

Adenosine has been shown to inhibit gastric acid secretion in the rat stomach, likely by regulating gastrin and somatostatin release. The current study demonstrates that A₁ and A₂[sub A] receptors may play significant roles in this action. Specifically, in the isolated vascularly perfused rat stomach, the effect of various selective adenosine agonists and antagonists suggests that the inhibition of immunoreactive gastrin (IRG) and somatostatin-like immunoreactivity (SLI) release is mediated by A₁ receptors, while the stimulation of SLI release is mediated by A₂[sub A] receptors. To determine the site at which adenosine acts to elicit these actions, immunohistochemistry was performed. Both A₁ receptor immunoreactivity (A₁R-IR) and A₂[sub A] receptor immunoreactivity (A₂[sub A]R-IR) were observed on mucosal somatostatin-containing D-cells. A₁R-IR was also observed on gastrin-containing G-cells, while neither A₁R-IR nor A₂[sub A]R-IR was observed on parietal cells. These results suggest that adenosine does not act directly on the parietal cells to inhibit gastric acid secretion. Instead, adenosine may act on Ai receptors of G-cells and D-cells to inhibit IRG and SLI release, respectively, and may act on A₂[sub A] receptors of D-cells to stimulate SLI release. The localization of A₁R-IR and A₂[sub A]R-IR in the gastric plexi suggests that adenosine may also act indirectly on the gastric plexi by altering enteric neural transmission to regulate IRG and SLI release. The coding regions of the gastric A₁ and A₂[sub A] receptors were also examined and found to be structurally identical to those in the rat brain, but expressed in extremely low levels. Gene expression was measured using Real-Time reverse-transcriptase polymerase chain reaction (RT-PCR) assays developed in the current study. Using these assays, A₁ and A₂[sub A] receptor gene expression was found to be altered by fasting and omeprazole treatment. These treatments produced reciprocal changes in A₁ receptor and gastrin gene expression, and similar changes in A₂[sub A] receptor and somatostatin gene expression. Further studies demonstrate that omeprazole treatment also altered adenosine agonist-induced changes in SLI release, suggesting that changes in adenosine receptor gene expression may result in actual changes in receptor expression. These results suggest that changes in the gastric state may alter A₁ and A₂[sub A] receptor expression, which in turn regulates the synthesis and release of gastrin and somatostatin, and consequently gastric acid secretion.

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