Thromboxane receptors can modulate gastric acid secretion in the rat.
The effects of PGE2 and the thromboxane A2 mimetic, U-46619, have been investigated on gastric secretion in the rat isolated gastric mucosa. Both compounds produced concentration-related inhibitions of histamine-induced secretion whereas only U-46619 inhibited methacholine-stimulated and basal secretion, and neither compound had any effect on the secretory response to dbcAMP. Indomethacin had no effect on the antisecretory activity of PGE2 but markedly reduced the potency of U-46619 suggesting that endogenous prostaglandins play a role in the U-46619 responses. However, direct inhibitory effects of U-46619 were seen at high concentrations. The thromboxane receptor antagonist AH23848, at concentrations selective for thromboxane receptors, had no effect on responses to PGE2 but markedly inhibited the effects of U-46619. We conclude that the antisecretory profile of U-46619 differs from that of PGE2. U-46619 has both direct and indirect antisecretory effects and these are mediated via thromboxane receptors in the rat gastric mucosa.
Reeves
J J
JJ
Department of Neuropharmacology, Glaxo Group Research Ltd., Herts, U.K.
Stables
R
R
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000527:Alprostadil / Q000627:therapeutic use*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D015232:Dinoprostone; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000502:physiology*; D017482:Receptors, Thromboxane; D013931:Thromboxanes / Q000037:antagonists & inhibitors
D001713:Biphenyl Compounds; D011450:Prostaglandin Endoperoxides, Synthetic; D011458:Prostaglandins E; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013931:Thromboxanes; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C046926:AH 23848; D000527:Alprostadil; D015232:Dinoprostone; D007213:Indomethacin