P 1(A 2/Ra)-Purinoceptors may Mediate the Stimulatory Effect of Adenosine and Adenosine Analogs on Acid Formation in Isolated Rabbit Parietal Cells

Abstract

The effects of adenosine (ADO) and its analogs 2-chloroadenosine (2CADO) and 5′-N-ethyl-carboxamido adenosine (NECA) on acid production, as measured by the [ 14C]-aminopyrine (AP) accumulation method, were studied in rabbit gastric parietal cells prepared by enzymatic dispersion and enriched by counterflow elutriation. ADO (1 μM to 1 mM), 2CADO (1 μM to 1 mM) and NECA (0.1 μM to 100 μM) caused significant concentration-related increases on AP uptake by resting parietal cells. The order of potency was NECA⪢2CADO≥ADO. Histamine and dibutyryl-cAMP (db-cAMP), known secretagogues, stimulated AP accumulation. In both, histamine- and db-cAMP-stimulated parietal cells, ADO, 2CADO and NECA at the above concentration ranges induced concentrationrelated increases of the respective AP accumulation raised-rates. The rank order of potency in both stimulated conditions was: NECA>2CADO⪢ADO. Cimetidine, a well known H 2 histamine receptor antagonist, at concentration of 100 μM caused potent inhibition of histamine-stimulated AP accumulation without affecting the stimulatory responses to db-cAMP. The increases of AP accumulation elicited by NECA, the most potent purine tested, in both resting and histamine- or db-cAMP-stimulated parietal cells were not significantly modified by cimetidine 100 μM. Theophylline (0.1 μM to 10 μM), a non-specific P 1-purinoceptor antagonist, caused significant inhibition of the NECA responses in both resting and histaminestimulated parietal cells. The concentration order of potency of theophylline was: 0.1 μM>1 μM>10 μM. These results suggest that there are P 1(A 2/Ra)-purinoceptors on rabbit parietal cells which mediate the stimulatory effects of adenosine and analogs on gastric acid production.