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 imp ortant pre-epithelial protective barrier against autodigestion of the gastric mucosa by acid and pepsin. Evidence from several independent s tudies shows there is a continuous layer of resilient viscoelastic muc us gel adherent to the surface of the gastroduodenal mucosa. The media n 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 establish ing a pH gradient within the gel. In the duodenum, evidence supports t he mucus bicarbonate barrier as a major protective mechanism against a cid aggression. The adherent mucus gel, by acting as an effective 'per meability' barrier to pepsin, protects the underlying sensitive mucosa from digestion. However, pepsin slowly digests mucus gel at its lumin al surface to produce soluble degraded mucin. In a rat gastric damage model in vivo, pepsin in excess digests the gastric mucus barrier suff iciently rapidly to outweigh new mucus secretion and lead to breaching of the mucus barrier with the formation of small punctate ulcers in t he epithelium accompanied by mucosal haemorrhage. The mucus secretagog ue 16,16 dimethyl prostaglandin E(2) acid the muco-adhesive carbopol-p olyacrylate both fully protected the mucosa against pepsin damage by e nhancing the protective properties of the mucus barrier. Sucralfate an d 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 (mu cus degrading) activity in gastric juice and this is associated with a n impaired mucin polymeric structure and a weaker mucus barrier. This enhanced mucolysis can be explained by increased levels of pepsin 1 se cretion in peptic ulcer disease. Evidence from these studies supports (i) the adherent mucus layer as a major protective barrier against pep sin aggression in the stomach; (ii) that pepsin is a mucosal damaging agent per se under conditions where acid alone is ineffective; and (ii i) decreased resistance of the mucus barrier to pepsin aggression coul d be a factor in the aetiology of peptic ulcer disease.