Adenosine: a modulator of gastric acid secretion in vivo

We tested the hypothesis that there are adenosine receptors in the gastric fundus responsible for the modulation of acid secretion to secretagogues. We utilized anesthetized gastric fistula dogs and infused both the secretagogues (histamine, 0.5 microgram/min and methacholine, 1 microgram/min) and adenosine through the gastric artery supplying the fundus of the stomach to avoid systemic effects of the drug. Adenosine infused to a concentration of 30 microM inhibited histamine-stimulated acid secretion from 197 +/- 25 to 68 +/- 19 microEq/15 min and inhibited methacholine-stimulated acid secretion from 280 +/- 48 to 81 +/- 24 microEq/15 min. Intravenously infused theophylline to a plasma concentration of 17 micrograms/ml (94 microM) blocked the inhibitory effect of adenosine on gastric acid secretion but did not affect the inhibitory effect of prostaglandin E2 on gastric acid secretion. In contrast, the specific phosphodiesterase inhibitor RO 20 1724 did not alter the inhibitory effect of adenosine on gastric acid secretion. In addition to its effect on gastric acid secretion, adenosine was found to be a potent vasodilator of gastric blood vessels. Our data suggest that there are inhibitory adenosine "R" receptors in the gastric fundus that modulate acid secretion to both histamine and methacholine.