Effect of adenosine 5'-triphosphate on secretagogue-stimulated (14C)-aminopyrine accumulation by rabbit isolated gastric glands.

The effect of adenosine 5'-triphosphate (ATP) on gastric acid secretion stimulated by histamine, carbachol and dibutyryl-cAMP (db-cAMP) was studied using glands isolated from rabbit gastric mucosa. The (14C)-aminopyrine (AP) accumulation method was used as an index of acid production by the gastric glands. Histamine-stimulated AP accumulation was significantly inhibited by ATP (10 mumol/l-1 mmol/l). The inhibitory action of ATP appeared to be specific, inasmuch as this nucleotide had no significant effect on basal secretion or secretion stimulated by carbachol or db-cAMP. The antisecretory effect of ATP on histamine-stimulated glands was not affected by the P1-purinoceptor antagonist, theophylline. Pretreatment of glands with indomethacin, a well known prostaglandin synthesis inhibitor, led to a significant reduction of the inhibitory responses to ATP. These results show that ATP inhibits the histamine-stimulated AP accumulation by rabbit isolated gastric glands and suggest that this effect is not due to an ectoenzymatic conversion of ATP into adenosine but to a direct effect of ATP which may be mediated via a P2-purinoceptor subtype linked to prostaglandin production.