GASTRIC-MUCOSAL ENDOGENOUS PROSTANOIDS ARE INVOLVED IN THE CELLULAR-REGULATION OF ACID-SECRETION FROM ISOLATED PARIETAL-CELLS

The effect of the cyclooxygenase inhibitor, indomethacin, was studied on histamine- and carbachol-induced [C-14]aminopyrine (AP) accumulation in isolated rabbit gastric parietal cells. A 10-min preincubation period with 200 muM indomethacin enhanced AP accumulation caused by 0.1 mM histamine (3.5 x) or by 0.1 mM 3-isobutyl-1-methylxanthine (1.8 x), and this effect was reversed by addition of 10 muM misoprostol [a stable PG (prostaglandin)E1 analog]. This suggests that endogenous PGs from the E series are involved in the down regulation of histamin-induced AP accumulation. In contrast, the same preincubation of cells with 200 muM indomethacin reduced carbachol-stimulated AP accumulation and this inhibition was not reversed by adding misoprostol. Moreover, this inhibitory effect on carbachol-induced AP accumulation was enhanced (80% inhibition) after preincubation with indomethacin, suggesting that prostanoids other that PGs from the E series may also regulate carbachol-induced AP accumulation. This was supported by the fact that carbachol released PGE2 from parietal cells and that this release was blocked by pretreatment with indomethacin. We concluded that: 1) endogenous prostanoids down regulate histamine-stimulated acid secretion; 2) PGs from the E series inhibited carbachol-stimulated acid secretion; and 3) carbachol stimulated the production of PGE2 and probably of other prostanoids in parietal cells which in turn stimulated carbachol-induced acid secretion.