The objectives of this proposal are to investigate the roles of gastrointestinal hormones (GIH) in the digestive processes. We will compare bioassay and radioimmunoassay (RIA) measurements of secretin and CCK. We will test the effects of divalent cations and of Cl ions on release of GIH. We will localize and characterize GIH in nerve tissue by bioassay and RIA. We will study the pattern of developmental appearance of GIH in neonatal animals and determine the effect of perinatal injection of trophic agents on that pattern; we will study the appearance of receptors for GIH during perinatal development and we will develop methods for identifying putative receptors for GIH in normal and neoplastic tissue. We will study the effect of epidermal growth factor (EGF) on pancreatic secretion and on the release of GIH. We will develop a RIA for EGF. We plan to study the effect of GIH and EGF on tumor growth and on growth of normal cell cultures. We plan to study the mechanisms of feedback inhibition of pancreatic enzyme secretion and their effects on GIH; we will measure the relative contributions of physiologic levels of various GIH to pancreatic secretion; we will study the effect of chronic administration of bombesin on GIH and on growth of the pancreas and duodenum; we plan to determine the effects on infusion of pancreatic polypeptide (PP) on pancreatic secretion and release of GIH; we will determine the effect of adrenocortical steroids on pancreatic secretion and GIH and will measure adrenocortical hormone receptors; we will study differences in PP secreted in the blood as compared with PP secreted into pancreatic juice. We plan to compare nutritional effects of total gastrectomy in Zollinger-Ellison and non-Zollinger-Ellison patients; we will compare long-term effects of selective proximal vagotomy on acid secretion and GIH release with those obtained from other operations for duodenal ulcer; we will measure basal and stimulated levels of GIH in patients with acute and chronic pancreatitis. we plan to generate monoclonal antibodies to GIH, and to develop techniques to separate, identify and characterize different molecular forms of GIH by physical means. We will study synthesis of GIH in mucosal cell cultures.
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