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- 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

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

“…The concentration of the drug solution and the rate of the drug infusion pump were calculated to achieve the desired final drug concentration that reached the stomach. The final concentration of dimethyl sulfoxide in the perfusate was less than 0.5%, which has been shown not to alter gastric peptide release (Yip and Kwok, 2004). Termination of drug infusion was achieved by disconnecting the drug solution syringe from the aortic cannula and stopping the drug infusion pump.…”

“…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).…”

“…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 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].…”

Purinergic receptors and gastrointestinal secretomotor function

“…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].…”