A. Choquet et al., GASTRIC-MUCOSAL ENDOGENOUS PROSTANOIDS ARE INVOLVED IN THE CELLULAR-REGULATION OF ACID-SECRETION FROM ISOLATED PARIETAL-CELLS, The Journal of pharmacology and experimental therapeutics, 266(3), 1993, pp. 1306-1311
The effect of the cyclooxygenase inhibitor, indomethacin, was studied
on histamine- and carbachol-induced [C-14]aminopyrine (AP) accumulatio
n in isolated rabbit gastric parietal cells. A 10-min preincubation pe
riod 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 sta
ble PG (prostaglandin)E1 analog]. This suggests that endogenous PGs fr
om the E series are involved in the down regulation of histamin-induce
d AP accumulation. In contrast, the same preincubation of cells with 2
00 muM indomethacin reduced carbachol-stimulated AP accumulation and t
his inhibition was not reversed by adding misoprostol. Moreover, this
inhibitory effect on carbachol-induced AP accumulation was enhanced (8
0% inhibition) after preincubation with indomethacin, suggesting that
prostanoids other that PGs from the E series may also regulate carbach
ol-induced AP accumulation. This was supported by the fact that carbac
hol released PGE2 from parietal cells and that this release was blocke
d 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 pr
ostanoids in parietal cells which in turn stimulated carbachol-induced
acid secretion.