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Am J Physiol Gastrointest Liver Physiol 277: G375-G382, 1999;
0193-1857/99 $5.00
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Vol. 277, Issue 2, G375-G382, August 1999

Adherent surface mucus gel restricts diffusion of macromolecules in rat duodenum in vivo

Gunnar Flemström1, Anneli Hällgren1, Olof Nylander1, Lars Engstrand2, Erik Wilander3, and Adrian Allen4

Departments of 1 Physiology and 3 Pathology, Uppsala University, SE-751 23 Uppsala, Sweden; 2 Swedish Institute for Infectious Disease Control, SE-105 21 Stockholm, Sweden; 4 Department of Physiological Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom

The aim of this study was to investigate the permeability of the adherent mucus gel layer in rat duodenum in vivo to macromolecules applied in the lumen. Rats were anesthetized with thiobarbiturate, and the duodenum was perfused with isotonic NaCl solution containing large-molecular-size secretagogues. Effects on mucosal HCO-3 secretion and blood-to-lumen 51chromium-labeled EDTA clearance were used as indexes that compounds had migrated across the mucus layer. Exposure to a low concentration of papain (10 U/100 ml) for 30 min removed the mucus layer without damage to the epithelium and induced or markedly enhanced HCO-3 secretory responses to cholera toxin (molecular mass of 85 kDa) or glucagon (3.5 kDa). Water extracts from a VacA cytotoxin (89 kDa) producing Helicobacter pylori strain, but not from a toxin-negative isogenic mutant, caused a small increase in HCO-3 secretion but only after the mucus layer had been removed by papain. The duodenal surface mucus gel thus significantly restricts migration of macromolecules to the duodenal surface. Release of bacterial toxins at the cell-mucus interface may enhance or be a prerequisite for their effects on the gastrointestinal mucosa.

cholera toxin; chromium-labeled EDTA clearance; glucagon; duodenal bicarbonate secretion; Helicobacter pylori; prostaglandin E2; VacA cytotoxin


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