This on-going investigation of intestinal electrolyte transport in health and disease is directed toward increasing our understanding of the regulation of intestinal ion transport by both neural agonists and hormonal agents. One series of investigations are directed toward understanding the mechanism by which opioid peptides affect intestinal ion transport. Previous studies in the past year established that met-enkephalin markedly increases sodium and chloride absorption in the ileum of the rabbit. These studies do not provide understanding as to the mechanism. Since specific opiate receptors are not present on ileal enterocytes and tetrodotoxin completely inhibited the effect of enkephalins on ion transport, an intermediary substance is believed responsible for their effect. Proposed studies will evaluate the possible role of calcium and various endogeneous humoral agonists as potential intermediates. Other studies are directed at identifying specific membrane receptors for agents that either increase intestinal absorption or stimulate secretion. In these proposed studies, specific receptor sites for somatostatin, calcitonin, prostaglandin, and insulin will be evaluated in both isolated colonic and ileal epithelial cells. These studies will increase our understanding of the regulatory control of intestinal electrolyte transport, should improve our understanding of the mechanism of diarrhea and provide insight into potential therapeutic intervention.