Mucus-bicarbonate barrier--shield or sieve.

It is now almost 30 years since Heatley' first published his mathematical model of the mucus barrier to acid-pepsin attack. At that time, techniques were not available to evaluate the components of his model and the existence of a pH gradient across mucus gel, sustaining the cell surface at near neutral pH despite luminal acid, could not be confirmed. During the last decade advances in technology, coupled with the development of potent inhibitors of gastric acid secretion have allowed definition of the components of the mucus-bicarbonate barrier together with confirmation of the existence of a pH gradient from lumen to epithelial cell surface.2 The molecular structure of mucus gel glycoprotein has been identified and methods developed for measuring gel thickness in unfixed mucosal samples.5 The existence of alkali secretion by gastric and proximal duodenal mucosa has been shown in a number of species, including man, and the mechanisms of bicarbonate transport explored.6 Finally, using pH sensitive microelectrodes the existence of a pH gradient, remarkably similar to that proposed by Heatley, has been shown across gastric and duodenal mucus gel in animals and man.78 Experiments have also been conducted to evaluate the functional significance of this mucus-bicarbonate barrier. Damaging agents, such as bile salts and non-steroidal anti-inflammatory drugs, inhibit gastric alkali secretion and reduce the magnitude of the mucus pH gradient." "' In contrast, protective prostaglandins either increase alkali secretion and the magnitude of the pH gradient or prevent the detrimental effects of bile salts and non-steroidal anti-inflammatory drugs.9 '0There is also evidence that the magnitude of gastric and duodenal alkali secretion may be influenced by the luminal environment. Animal and human studies have shown that increasing luminal acidity results in increased alkali secretion, suggesting the existence of an autoregulatory mechanism that adjusts the mucus-bicarbonate barrier to prevailing luminal acidity." 12 More recently investigators have explored the possibility that ulcer healing drugs may act by enhancing the mucus-bicarbonate barrier. In this issue of Gut, Professor Konturek and coworkers present evidence that the healing action of colloidal bismuth (De-Nol) may be partly mediated by its stimulatory effects on gastroduodenal alkali secretion and local prostaglandin metabolism.'3 There is also evidence that sucralfate (Antepsin) and the aluminium component of certain antacids have similar actions on alkali secretion and mucosal prostaglandin synthesis.'4 The inference from such observations is that there is a relationship between the ulcer healing actions of these drugs and their effects on …