The Effect of Arachidonic Acid and Its Metabolites on Acid Production in Isolated Human Parietal Cells

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Abstract
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 10−5M) was significantly inhibited by prostaglandin (PG) E2 to 66 ± 7% at 10−8M, 42 ± 8% at 10−6M, and 13 ± 10% at 10−4 M (mean ± SEM, n = 10). PGF2α, PGD2, and PGI2 showed significant inhibitory effects only at very high concentrations (10−5-10−4M). 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 < 0.02, n = 10), and the histamine-stimulated (10−5M) acid production from 100% to 64 ± 7.2% (p < 0.001, n = 10). Aspirin (10−3 M) increased basal (45 ± 9.6%, p < 0.001, n = 10) and histamine-stimulated (10−6 M) acid production (164 ± 16.3%, p < 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.