EXPERIMENTAL STUDIES OF INTESTINAL ION AND WATER TRANSPORT

A major advance in transport physiology was H. H. Ussing's development of the voltage-clamp method, and later the Koefoed-Johnsen-Ussing mod el for Na+ transport. In the same decade, J. C. Skou identified the Na +-K+-ATPase, which maintains the Na+ and K+ gradients that drive most epithelial transport processes. With this foundation, Danish scientist s have pursued the mechanism of ion transport and the resulting solute -linked water flow. Recent contributions have been on isosmotic transp ort, suggesting solute recycling, and KCl-water cotransport in the bas olateral epithelial cell membrane. Efficient small intestinal nutrient absorption is dependent on coupling to the Na+ gradient. Cotransport of Na+ and glucose is quantitatively the most important absorptive mec hanism in the small intestine, as illustrated by the success of oral r ehydration solutions in diarrhoea. The majority of amino acids are lik ewise transported by Na+ dependent carriers, but recent experiments ha ve identified a concomitant Cl- dependency for some. Regulation of int estinal secretion, both under normal digestive processes, and in respo nse to enterotoxins, has turned out to be very complex. It involves lo cal and central neuronal regulation through an array of neurotransmitt ers and local actions of gastrointestinal hormones. Major effectors ar e the submucosal neurons and the main transmitters serotonin, vasoacti ve intestinal peptide, acetylcholine, substance P, and neurotensin. De velopment of antisecretagogues is impeded by the existence of several receptor subtypes and significant species differences. The Na+ and wat er-conserving properties of the large intestine have been shown to be regulated by adrenocortical hormones, with aldosterone as a potent sti mulator of colonic Na+ absorption. A major colonic function is the sym biosis with the anaerobic bacterial population. The fermentation of ca rbohydrate to short-chain fatty acids, which can be absorbed, suppleme nts small intestinal digestive function.