Mechanisms underlying gastric mucosal damage induced by indomethacin and bile-salts, and the actions of prostaglandins.
1 The mechanisms by which -he bile salt, sodium taurocholate, potentiates the formation of gastric mucosal erosions induced by indomethacin has been investigated in the rat. 2 Systemic administration of indomethacin lowered resting mucosal blood flow but had no effect on the acid back-diffusion across the mucosa. 3 Gastric perfusion of taurocholate in acid solution increased acid back-diffusion and lowered the potential differences. This was accompanied by an increase in mucosal blood flow, which may represent a protective mechanism in the mucosa. 4 Administration of indomethacin during acid-taurocholate perfusion reduced this elevated mucosal blood flow without any further change in acid back-diffusion. 5 The results suggest that although a decrease in mucosal blood flow or an increase in acid back-diffusion can lead to a low incidence of erosions, a combination of both produces extensive mucosal damage. 6 The (15S)-methyl analogue of prostaglandin E2 reduced erosion formation induced by indomethacin and acid-taurocholate administration. 7 It is suggested that this protective action of the prostaglandin analogue may be linked to changes in gastric mucosal permeability and in mucosal blood flow.
D000143:Acids / Q000378:metabolism; D000818:Animals; D004058:Diffusion; D004347:Drug Interactions; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D011458:Prostaglandins E / Q000494:pharmacology*; D011465:Prostaglandins, Synthetic / Q000494:pharmacology; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D013656:Taurocholic Acid / Q000494:pharmacology*
D000143:Acids; D011458:Prostaglandins E; D011465:Prostaglandins, Synthetic; D013656:Taurocholic Acid; D007213:Indomethacin