The effect of arachidonic acid and its metabolites on acid production in isolated human parietal cells.

The effect of arachidonic acid and its metabolites on the histamine-stimulated acid production in human isolated parietal cells provenient from endoscopic biopsies was examined. 14C-aminopyrine (14C-AP) accumulation in the parietal cells was used for evaluation of acid production. Histamine dose-dependently increased AP uptake. Histamine stimulation (taken as 100% at 10(-5) M) was significantly inhibited by prostaglandin (PG) E2 to 66 +/- 7% at 10(-8) M, 42 +/- 8% at 10(-6) M, and 13 +/- 10% at 10(-4) M (mean +/- SEM, n = 10). PGF2 alpha, PGD2, and PGI2 showed significant inhibitory effects only at very high concentrations (10(-5)-10(-4) M). Leukotriene (LT) B4 and LTC4 were without effect. The basal acid production (taken as 0%) was lowered significantly by 10(-6) M arachidonic acid to -20 +/- 7.4% (p less than 0.02, n = 10), and the histamine-stimulated (10(-6) M) acid production from 100% to 64 +/- 7.2% (p less than 0.001, n = 10). Aspirin (10(-3) M) increased basal (45 +/- 9.6%, p less than 0.001, n = 10) and histamine-stimulated (10(-6) M) acid production (164 +/- 16.3%, p less than 0.001). It is concluded that PGE2, the major product from arachidonic acid metabolism in the human gastric mucosa, is a significant inhibitor of the histamine-stimulated human parietal cell and may, in humans, play a role as a local physiologic inhibitor of acid secretion.