THE GASTRODUODENAL MUCUS BARRIER AND ITS ROLE IN PROTECTION AGAINST LUMINAL PEPSINS - THE EFFECT OF 16,16-DIMETHYL PROSTAGLANDIN-E(2), CARBOPOL-POLYACRYLATE, SUCRALFATE AND BISMUTH SUBSALICYLATE

Mucus and bicarbonate secretions have been widely implicated as an important pre-epithelial protective barrier against autodigestion of the gastric mucosa by acid and pepsin. Evidence from several independent studies shows there is a continuous layer of resilient viscoelastic mucus gel adherent to the surface of the gastroduodenal mucosa. The median thickness of the adherent gastric mucus layer in humans is 180 mu m, range 50-450 mu m. The epithelial bicarbonate secretion permeates the unstirred matrix of mucus gel neutralizing luminal acid and establishing a pH gradient within the gel. In the duodenum, evidence supports the mucus bicarbonate barrier as a major protective mechanism against acid aggression. The adherent mucus gel, by acting as an effective 'permeability' barrier to pepsin, protects the underlying sensitive mucosa from digestion. However, pepsin slowly digests mucus gel at its luminal surface to produce soluble degraded mucin. In a rat gastric damage model in vivo, pepsin in excess digests the gastric mucus barrier sufficiently rapidly to outweigh new mucus secretion and lead to breaching of the mucus barrier with the formation of small punctate ulcers in the epithelium accompanied by mucosal haemorrhage. The mucus secretagogue 16,16 dimethyl prostaglandin E(2) acid the muco-adhesive carbopol-polyacrylate both fully protected the mucosa against pepsin damage by enhancing the protective properties of the mucus barrier. Sucralfate and bismuth subsalicylate were partially effective in protection against pepsin damage but this protection was mainly mediated at the level of the mucosa. In peptic ulcer disease, there is increased mucolytic (mucus degrading) activity in gastric juice and this is associated with an impaired mucin polymeric structure and a weaker mucus barrier. This enhanced mucolysis can be explained by increased levels of pepsin 1 secretion in peptic ulcer disease. Evidence from these studies supports (i) the adherent mucus layer as a major protective barrier against pepsin aggression in the stomach; (ii) that pepsin is a mucosal damaging agent per se under conditions where acid alone is ineffective; and (iii) decreased resistance of the mucus barrier to pepsin aggression could be a factor in the aetiology of peptic ulcer disease.