Role of Adenosine A₁ Receptor in the Regulation of Gastrin Release

Abstract

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 M and maximally inhibited IRG release at 1 M. At concentrations of 0.001 to 0.1 M, the A 2A receptorselective agonist 2-p-(2-carboxyethyl)phenethylamino-5Ј-Nethylcarboxamidoadenosine and A 3 receptor-selective agonist, 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 transcriptionpolymerase 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.

Involvement of Adenosine Signaling in Controlling the Release of Ghrelin from the Mouse Stomach

“…The concentrations used for adenosine and its receptor-selective agonists, and EHNA were previously shown to have significant effects on gastric peptide release in mouse and rat stomachs (Kwok et al, 1990;Yip and Kwok, 2004;Yip et al, 2004b;Yang et al, 2009). The concentrations of the adenosine receptor antagonists, ZM 241385 and DPCPX, used in this study have also been shown to abolish the adenosine A 2A and A 1 receptor-mediated action on peptide release in rodent stomachs, respectively (Yip and Kwok, 2004;Yip et al, 2004b;Yang et al, 2009).…”

“…The abundance of adenosine receptors in the stomach suggests that adenosine may play a role in regulating the release of various gastric peptides (Yip and Kwok, 2004;Yip et al, 2004a,b;Yang et al, 2009). We have demonstrated previously that adenosine stimulates somatostatin release via activation of A 2A receptors in both the rat stomach (Yip and Kwok, 2004) and the mouse stomach (Yang et al, 2009) and inhibits gastrin release via activation of the A 1 receptors in the rat stomach (Yip et al, 2004b). However, immunohistological studies show that not all adenosine A 1 or A 2A receptors are colocalized with gastrin-and somatostatin-containing cells (Yip and Kwok, 2004;Yip et al, 2004b), suggesting that adenosine may also modulate the release of other gastric peptides.…”

Purinergic receptors and gastrointestinal secretomotor function

“…Adenosine analogs augment somatostatin-like immunoreactivity release with a potency profile of CGS 21680= 5′-N-ethylcarboxamidoadenosine > 2-chlroadenosine > [125].…”

“…A1/gastrin release In the stomach, adenosine protects against stress-induced gastric ulcer formation by inhibiting gastric acid secretion by direct action on parietal cells in some species (guinea pigs and dogs, [42,48]) but not others (rats, [86] [123,125].…”

Purinergic signalling in the gastrointestinal tract and related organs in health and disease

“…It was later shown that adenosine may suppress immunoreactive gastrin release by activating A 1 receptors on G cells, leading to inhibition of gastric acid secretion [739]. Adenosine may also act via A 2A receptors to augment somatostatin release and consequently influence gastric acid secretion [732,738].…”