Effects of Arachidonic Acid on Rat Gastric Acid Secretion in Response to Different Secretogogues; Inhibition of These Effects by Indomethacin

Abstract

1 The effects of the prostaglandin precursor, arachidonic acid, and the non-steroidal antiinflammatory drug, indomethacin, on gastric acid secretion were studied in the rat, in vivo and in vitro. Gastric mucosal blood flow was also measured in vivo.2 Arachidonate produced significant inhibition of acid secretion stimulated by pentagastrin or histamine. It did not significantly affect dibutyryl cyclic adenosine 3',5'-monophosphate (db cyclic AMP) induced acid secretion. 3 Inhibition of acid secretion by arachidonate was accompanied by a rise in the ratio of mucosal blood flow to acid secretion. 4 Indomethacin did not significantly alter histamine-or pentagastrin-induced acid secretion. 5 In the presence of indomethacin, the inhibitory effect of arachidonate was significantly reduced. 6 These results provide evidence that the rat gastric mucosa is capable of synthesizing, from exogenous precursor, products of cyclo-oxygenase which inhibit gastric acid secretion.

The inhibitory effects of 5‐hydroxytryptamine on gastric acid secretion by the rat isolated stomach

“…It has been shown previously that PGE2 inhibits the response to pentagastrin but not isoprenaline in this preparation . Other workers, using different isolated stomach preparations, have reported that prostaglandin derivatives do not inhibit the response to db cyclic AMP and have inconsistent effects on cholinergic stimulation (Main & Pearce, 1978;Frame & Main, 1980;Boughton-Smith & Whittle, 1981). Thus there are similarities in the inhibitory effects of 5-HT and prostaglandins but they are not identical.…”

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

“…Indomethacin, an inhibitor of prostaglandin synthesis has been found to potentiate acid secretion induced by pentagastrin in the anaesthetized rat and this might indicate an inhibitory role of prostaglandins in the rat stomach. However, in other studies indomethacin had no effect on basal, pentagastrin or histamine-stimulated acid secretion but resulted in a potentiation ofdibutyryl adenosine 3': 5'-cyclic monophosphate (db cyclic AMP)-induced secretion in vitro (Main & Pearce, 1978;Frame & Main, 1980;Donaldson & Main, 1981). This was surprising since prostaglandins lower intracellular cyclic AMP levels in parietal cells (Major & Scholes, 1978;Soll, 1980) but do not inhibit gastric acid secretion induced by exogenous db cyclic AMP (Main & Pearce, 1978 (Kennedy et al, 1982) in an attempt to identify the prostanoid receptor mediating the inhibition ofgastric acid secretion.…”

“…It is well established that prostaglandins, particularly of the E series, are potent inhibitors of gastric acid secretion in many species including rat (Frame & Main, 1980;Boughton-Smith & Whittle, 1981), dog (Robert et al, 1967) and man (Karim et al, 1973;Konturek et al, 1976). Although the inhibition of acid secretion in the rat is well documented no attempt has been made to classify the prostaglandin receptor mediating this response.…”

Effects of Cyclooxygenase-1 and -2 Inhibition on Gastric Acid Secretion and Cardiovascular Functions in Rats

“…However, the effect of NSAIDs on gastric acid secretion has been the object of much debate. Most studies have mainly examined the effect of indomethacin and have shown either no effect [24][25][26][27][28][29][30][31] , or stimulatory [24,27,29,[32][33][34][35][36] or actually inhibitory effects [36] of this compound on acid production, depending on the species, secretory stimulus or experimental model used. Only few studies have focused on the effect of selective COX-1 or COX-2 inhibitors and results are not conclusive.…”