Inhibitory action of extracellular adenosine 5'-triphosphate on parietal cells isolated from rabbit gastric mucosa

The effects of the purine nucleotides, adenosine 5'-triphosphate (ATP) and their analogs 2-methylthio ATP and beta,gamma-methylene ATP, as well as those of the pyrimidine nucleotide, uridine 5'-triphosphate (UTP), on acid production in isolated rabbit gastric parietal cells prepared by enzymatic dispersion and enriched by counterflow elutriation were studied. The (C-14)-aminopyrine (AP) accumulation method was used as an index of acid production by the parietal cells. In histamine-stimulated parietal cells, ATP and 2-methylthio ATP, but not beta,gamma-methylene ATP or UTP, produced significant and concentration-related inhibition of the histamine-stimulated AP uptake. The rank order of potency of these nucleotides in inhibiting histamine-stimulated AP accumulation was 2-methylthio ATP > ATP >> beta,gamma-methylene ATP, UTP. In contrast to these results, the AP accumulation responses to secretagogues other than histamine such as carbachol and dibutyryl-cAMP, were not significantly modified by ATP and analogs. Pretreatment of parietal cells with indomethacin, a prostaglandin synthesis inhibitor, led to a significant reduction of the inhibitory responses elicited by ATP on histamine-stimulated AP uptake. These data suggest that ATP selectively inhibits the histamine-stimulated gastric acid secretion in rabbits by acting directly on parietal cells; that a component of this action seems to be related with a stimulation of prostaglandin production and that the antisecretory effect of ATP on isolated rabbit parietal cells may be mediated via P-2Y-purinoceptors.