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 [14C]aminopyrine (AP) accumulation in isolated rabbit gastric parietal cells. A 10-min preincubation period with 200 microM 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 microM misoprostol [a stable PG (prostaglandin)E1 analog]. This suggests that endogenous PGs from the E series are involved in the down regulation of histamine-induced AP accumulation. In contrast, the same preincubation of cells with 200 microM 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 than 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.
Laboratoire de Biochimie des Membranes, Institut National de la Santé et de la Recherche Médicale CJF 9207, Faculté de Pharmacie, Montpellier, France.
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A
Choquet
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Magous
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JP
Bali
D000632:Aminopyrine / Q000493:pharmacokinetics; D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology; D010295:Parietal Cells, Gastric / Q000166:cytology / Q000378:metabolism*; D011453:Prostaglandins / Q000502:physiology*; D011817:Rabbits
D011453:Prostaglandins; D000632:Aminopyrine; D015232:Dinoprostone; D007213:Indomethacin