Since Somatostatin stimulates water and electrolyte absorption in the intestine and prevents secretion induced by secretagogues, I wish to determine how this happens and whether it has any clinical significance. Thus, the major objective of this proposal is to determine the site and the mechanism of this anti-secretory action. The minor objective will be to determine the effectiveness of somatostatin in the treatment of diarrhea associated with endocrine tumors. Direct receptor binding studies and indirect studies of the biological resonses to somatostatin will be performed using isolated intestinal cells, plasma membrane preparations, and whole tissues. This part of the study will tell us whether there are receptors on the epithelial cells or on other cell types. I will also investigate the intracellular mechanism of action, including the effect of somatostatin on calcium and calmodulin concentration in the epithelial cells. Interaction of somatostatin with histamine and prostaglandin will be studied to determine their possible role in somatostatin action. The effect of somatostatin on passive permeability will also be studied. Finally, if patients with endocrine tumors associated with diarrhea are available, I will study the clinical efficacy of somatostatin in this condition.