Physiological regulation of epithelial junctions in intestinal epithelia.

This symposium paper is a digest of three full-length manuscripts currently in press with J Membrane Biology (see reference list). The three papers provide evidence that sugars, amino-acids and small peptides are transported through intestinal epithelium primarily by solvent drag through paracellular channels. Active transport of sugars and amino acids plays a necessary but nevertheless secondary role in the mass transport from intestinal lumen to blood at physiological concentrations. Na-coupled solute transport serves two principal functions - a) it inserts relatively small amounts of solutes at high concentration into the intercellular spaces below the occluding junctions thereby providing the force for osmotic flow and solvent drag; b) it triggers contraction of the perijunctional actomyosin ring, thereby widening the occluding junctions and providing optimal conditions for transport of luminal nutrients in bulk by solvent drag. Active transport of glucose reaches its maximum capacity (V max) at luminal concentrations of 10-15 mM whereas transport by solvent drag increases in proportion to luminal concentration; at concentrations normally present in the duodenum and upper jejunum after a meal (50-300 mM) transport through paracellular spaces by solvent drag accounts for 60-90% of total glucose absorbed into blood. Similar considerations apply to other hydrophilic nutrients including amino acids, small saccharides and peptides. As nutrients are removed from the upper intestine by the above mechanisms, their concentrations decrease and the "traditional" role of active transport becomes a greater fraction of total absorption.(ABSTRACT TRUNCATED AT 250 WORDS)