Lack of Direct Effect of Adenosine on the Parietal Cell Function in the Rat

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.

Section: Discussionsupporting

confidence: 82%

mentioning

confidence: 95%

Role of Adenosine A₁ Receptor in the Regulation of Gastrin Release

Yip

Leung²,

Kwok³

2004

“…In fact, in guinea pigs (Helds-inger et al, 1986) and dogs (Gerber et al, 1985), adenosine inhibits acid secretion by acting directly on the acid-secreting parietal cells. However, in rats, the acid-inhibitory action of adenosine is unlikely to be direct because administration of adenosine and its analogs did not alter aminopyrine uptake in parietal cell preparations (Puurunen et al, 1987). Instead, our laboratory has shown that in rats, adenosine can suppress acid secretion indirectly by inhibiting the release of the acid secretagogue, gastrin (Yip et al, 2004b), as previously demonstrated in canine antral G-cells (Gerber and Payne, 1988).…”

supporting

confidence: 47%

Regulation of Somatostatin Release by Adenosine in the Mouse Stomach

Yang

Chen²,

Kieffer³

et al. 2009

Adenosine inhibits gastric acid secretion, either directly by acting on acid-secreting parietal cells or indirectly by stimulating the release of the acid inhibitor, somatostatin. The present study examined the role of adenosine on somatostatin release in an isolated vascularly perfused mouse stomach model. Concentrations of exogenous adenosine Ն 1.0 M stimulated gastric release of somatostatin-like immunoreactivity (SLI), and this effect was blocked by the A 2A receptor antagonist ZM 241385augmented SLI release in a concentrationdependent manner, suggesting that A 2A receptor activation is involved in the stimulatory effect of adenosine on SLI release. Conversely, SLI release was inhibited by the A 1 receptor agonists N 6 -cyclopentyladenosine and 2-chloro-N 6 -cyclopentyladenosine and lower concentration of adenosine (0.01 M). The involvement of specific adenosine receptors in controlling the release of gastric SLI was also examined using A 2A receptor knockout (A 2A R-KO) mice. In these mice, adenosine (10 M) inhibited SLI release, and the effect was abolished by the selective A 1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, suggesting a link between the selective A 1 activation and inhibition of SLI release. The adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride augmented SLI release in wild-type controls but not in the presence of ZM 241385 or in A 2A R-KO mice. We conclude that adenosine has dual actions on regulating mouse gastric SLI release: stimulatory at higher concentrations through the A 2A receptor and inhibitory at lower concentrations through the A 1 receptor, whereas A 2B and A 3 receptors have a minimal role.

“…In addition to this direct action, adenosine has also been shown to inhibit the secretion of the acid secretagogue gastrin from canine antral G-cells (Schepp et al, 1990). In rats, adenosine analogs did not alter basal or histamine-stimulated aminopyrine uptake in isolated enriched parietal cell preparations (Puurunen et al, 1987). Thus, in this species, adenosine most likely inhibits gastric acid secretion indirectly.…”

mentioning

confidence: 96%

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

Yip

Kwok²

2004

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- Adenosine has been demonstrated to modulate a variety of physiological functions by acting on purinergic P1 receptors. These G protein-coupled receptors are classified into adenosine A 1 , A 2A , A 2B , and A 3 subtypes based on their pharmacological and structural properties. Each subtype has been cloned in the brain tissues of various species, including human (Fredholm et al., 2001).Clinical studies have suggested that changes in the endogenous level of adenosine may influence gastric acid secretion and play a role in ulcer formation. The activity of adenosine deaminase (ADA), a metabolic enzyme of adenosine, seems to be directly correlated with basal and maximal levels of gastric acid output in the fundic mucosa of achlorhydria, gastritis, and ulcer patients (Namiot et al., 1990). Patients suffering from hypersecretion of gastric acid were shown to exhibit elevated levels of ADA activity. In gastric ulcer patients, ADA activity in the corpus mucosa was also shown to be reduced after ranitidine treatment (Namiot et al., 1991). These studies, therefore, suggest that adenosine inhibits gastric acid secretion and acts as a gastroprotective agent. Article, publication date, and citation information can be found at