The aims of these investigations are 1) to further define pathways of electrolyte transport in the intestine and how they are altered by disease states; and 2) determine the role of protein phosphorylation in the control of intestinal electrolyte transport. Specifically, we propose to define Na, Cl and HCO3 transport pathways across intestinal brush border and basolateral membrane utilizing highly enriched vesicular preparations of these membranes. Once these pathways have been defined, we will determine the effect of hormones, neurotransmittors, enterotoxins, and potential therapeutic drugs (that have effects in vivo or in vitro) on these transport pathways. Since there is some evidence that ion transport differs in crypt and villous cells, we will attempt to separate these two cell populations and determine ion transport in vesicular preparations of brush border and basolateral membrane. Since intracellular calcium activity profoundly affects ion transport, we will determine calcium transport pathways across the basolateral membrane utilizing the vesicular technique, and the effect of neurohumoral agents, enterotoxins and drugs on these pathways. Finally, we will determine the role of protein phosphorylation in the changes in ion transport induced by intracellular calcium and cyclic nucleotides.