It is our belief that digestion processes are brought about by the interactions between substances produced by the GI tract, pancreas and possibly the brain and that the role of a single peptide is downplayed by these interactions. The objective of this proposal is to investigate the crossreactivity and interactivity of these peptides. We plan to study by radioimmunoassay and by bioassay the chemical nature, biologic action, storage and release of CCK-like peptide found in brain and GI tract of several experimental animals. We will study the interrelationships between pancreatic endocrine and exocrine functions and the release and actions of GI and pancreatic hormones. We plan to study, continuously, the release and interactions of gastrointestinal and pancreatic hormones in animals in physiologic conditions over expanded periods of time. We plan to study the interrelationships between the release and biologic actions of GI and pancreatic hormones after neutralization of peptides with specific antibodies directed towards regions or towards all of the peptide molecule. We will study the effect of cigarette smoke and of chemical agents that are found in cigarette smoke on the release and actions of GI peptides and pancreatic endocrine and exocrine functions. We will conduct studies designed to generate specific antibodies by using the monoclonal antibody technique. These antibodies will be used to study the actions of GI peptides and to develop region specific radioimmunoassays. We will investigate the role of acute and chronic exogenous and endogenous cholecystokinin on satiety and sbusequent weight loss in rats and dogs. We will study the interrelations between hormones of gastrointestinal, pancreatic, pituitary and gonadal origin in experiments designed to determine if there is a centralized mechanism that controls the release and actions of gastrointestinal hormones. We plan to establish radioligand binding assays in order to identify cholecystokinin and pancreatic polypeptide receptors in target tissues of these peptides in several species of animals. We will conduct studies to optimize our existing radioimmunoassays and to develop and validate newer systems for peptides that are currently not measured in our laboratory.
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