INHIBITION OF ACID-SECRETION IN ISOLATED CANINE PARIETAL-CELLS BY PROSTAGLANDINS

Abstract

Isolated canine parietal cells were used to evaluate inhibition of acid secretion by both endogenously synthesized and exogenously added prostglandins (PG). Uptake of [14C]aminopyrine by the parietal cells was used as an index of acid secretion. The effect of increasing endogenous PG synthesis was determined by incubating arachidonic acid with histamine-stimulated parietal cells. Arachidonic acid (10-6 and 10-5 M) was a potent inhibitor of histamine-stimulated acid secretion. This effect of arachidonic acid was totally abolished when the cells were pretreated with 100 .mu.M indomethacin. The effect of exogenous, preformed PG on histamine-stimulated acid secretion was evaluated by adding PGE2, PGI2, PGF2 or PGD2 to parietal cells. PGE2 was the most potent inhibitor of acid secretion, with a 50% inhibition of maximal acid secretion (ID50) at 7.5 .times. 10-8 M. PGI2 and PGF2.alpha. also inhibited acid secretion but at higher concentrations. The ID50 for PGI2 and PGF2.alpha. was 10-5 M. PGD2 was inactive at inhibiting acid secretion. Both endogenous and exogenous PG inhibit acid secretion directly at the parietal cells, and PGE2 is most likely the PG produced locally to modulate parietal cell acid secretion.