Mechanisms underlying gastric mucosal damage induced by indomethacin and bile-salts, and the actions of prostaglandins

Br J Pharmacol. 1977 Jul;60(3):455-60. doi: 10.1111/j.1476-5381.1977.tb07522.x.

Abstract

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.

MeSH terms

  • Acids / metabolism
  • Animals
  • Diffusion
  • Drug Interactions
  • Gastric Mucosa / blood supply
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / metabolism
  • In Vitro Techniques
  • Indomethacin / pharmacology*
  • Membrane Potentials / drug effects
  • Prostaglandins E / pharmacology*
  • Prostaglandins, Synthetic / pharmacology
  • Rats
  • Regional Blood Flow / drug effects
  • Taurocholic Acid / pharmacology*

Substances

  • Acids
  • Prostaglandins E
  • Prostaglandins, Synthetic
  • Taurocholic Acid
  • Indomethacin