Characterization of the effects of adenosine, adenosine 5'-triphosphate and related purines on acid secretion in isolated rabbit gastric glands

Abstract

The influence of adenosine, AMP, ADP, ATP, the adenosine analogue L-PIA and the ATP analogue beta,gamma-methylene ATP, on gastric acid secretion, as measured by the aminopyrine accumulation method, in resting and histamine-stimulated glands isolated from rabbit gastric mucosa was studied. In resting glands, adenosine and its analogue L-PIA (10 microM-1 mM) caused significant concentration-related increases of the basal H+ secretion, whereas no changes were obtained in response to the other purines tested. In histamine-stimulated glands, adenosine, L-PIA and AMP (10 microM-1 mM) induced concentration-related increases of the H+ secretory rate, whereas ATP, beta,gamma-methylene ATP and ADP (10 microM-1 mM) produced concentration-related decreases of the H+ raised rate. The rank order of potency of the purine compounds in increasing the stimulated H+ secretion was: adenosine greater than L-PIA much greater than AMP, and in decreasing it was: ATP much greater than ADP greater than beta,gamma-methylene ATP. The stimulatory responses to adenosine were inhibited by theophylline (10 microM-100 microM) and caffeine (10 microM-1 mM); whereas, the inhibitory responses to ATP were significantly reduced by the well known prostaglandin synthesis inhibitor indomethacin (1 microM-100 microM). From the results it is concluded that in isolated rabbit gastric glands, purine compounds are effective modulators of the gastric H+ secretory process. The pattern of purine activity obtained suggests that the stimulatory responses, inhibited by methylxanthines, may be mediated via P1-purinoceptors, while the inhibitory responses, reduced by indomethacin, may be mediated via P2-purinoceptors.