Mucus glycoprotein structure, gel formation and gastrointestinal mucus function

Gastrointestinal mucus occurs as a water-insoluble gel adherent to the mucosal surfaces and as a viscous, mobile solution in the lumen. The adherent gastroduodenal mucus gel is part of the mucosal defence against acid (with HCO3-), pepsin (diffusion barrier) and mechanical damage. Rheological studies show that gastrointestinal mucus is a weak, viscoelastic gel. The size and physical properties of the isolated component glycoproteins depend critically on the methods used to obtain them. A glycoprotein preparation of Mr approximately 2 X 10(6), which possesses the gel-forming properties of the native mucus, is considered to represent the secreted covalent entity in pig gastric and small intestinal mucus. These glycoproteins have a polymeric structure of subunits joined by disulphide bridges between non-glycosylated regions of their protein cores. Glycoprotein polymerization, essential for gel formation, is deficient in gastric mucus in peptic ulcer disease. In vivo, adherent mucus gel forms a thin but continuous cover of variable thickness (rat 5-500 microns) over the gastroduodenal mucosa. Luminal pepsin rapidly dissolves this mucus cover and its continuity is maintained by fresh mucus secretion. Bile, HCl, 2 M-NaCl and ethanol (less than 40%) do not destroy mucus gel structure. Prostaglandins and carbachol increase mucus thickness, affording better protection, but it is thought that continuity of the protective mucus cover is the critical factor in its protective functions.