Effects of indomethacin, piroxicam and selected prostanoids on gastric acid secretion by the rat isolated gastric mucosa

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Abstract
1 The effect of the cyclo-oxygenase inhibitors indomethacin and piroxicam have been investigated on histamine- and dibutyryl cyclic AMP-induced acid secretion in the rat isolated gastric mucosa. The relative potencies of a number of prostanoids as inhibitors of histamine-induced acid secretion were determined in an attempt to classify the prostaglandin receptor mediating this response. 2 Indomethacin (8 .times. 10-9 -2.7 .times. 10-6 M) and piroxicam (3 .times. 10-6 M) potentiated the secretory response elicited by histamine. This effect might be due to inhibition of the biosynthesis of antisecretory prostanoids. Indomethacin (2.7 .times. 10-6 M) and piroxicam (3 .times. 10-6 M) also potentiated the secretory response to dibutyryl cyclic AMP, but since prostaglandin E2 (PGE2, 10-5 M) did not inhibit this secretory response, the mechanism of the potentiation may differ from that of histamine. 3 The potency of the thromboxane mimetic U-46619 as an inhibitor of histamine-induced acid secretion was markedly reduced in the presence of indomethacin, suggesting that U-46619 may release endogenous antisecretory prostanoids. 4 In the presence of indomethacin (2.7 .times. 10-6 M) all the prostanoids tested produced concentration-related inhibitions of histamine-induced gastric acid secretion. PGE-analogues were the most potent compounds, the rank order of potency being 16,16 dimethyl PGE2 > PGE2 > PGE2.alpha. > U-46619 > PGD2 > PGI2. This order of potency is very similar to that obtained in smooth muscle preparations containing ''EP'' receptors, suggesting that this receptor type also mediates inhibition of histamine-induced acid secretion in the rat.

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