IMMUNOLOGY AND DISEASES OF THE GASTROINTESTINAL TRACT

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This research proposal is directed to the study of gastrointestinal regula- tory peptides, with particular emphasis on gastrin, which plays a crucial role in the regulation of gastric acid secretion. Studies will utilize a variety of immunological and immunochemical techniques to examine content, release, and interrelationships of certain gastrointestinal regulatory peptides utilizing a variety of methods, including organ culture, animal models and in studies in man. Studies are designed to identify factors which participate in regulation of gastrin release, including somatostatin and gastrin releaseing peptide, a substance believed to be the mammalian equivalent of bombesin. Pulse-chase experiments will be formed with antral mucosa and gastrinoma tissue to identify potential precursor-product relationships of multiple molecular species of gastrin. In vitro and in vivo studies will be performed utilizing antibodies to various regulatory peptides, including antibodies to somatostatin, gastrin releasing peptide, and gastrin to analyze the potential role played by these peptides and their effects in mediation of other peptide effects. The effects of various nutrients on promotion of gastrointestinal regulatory peptide release and physiological effects will be determined, as will assessment of the nature of the molecular species of regulatory peptides released by different forms of feeding. Patients with duodenal ulcer often exhibit increased gastric acid secretion and a significant portion of these patients demonstrate increased gastrin release in response to feeding. Studies will be performed to examine the relationship between somatostatin and gastrin in antral mucosa of duodenal ulcer patients compared with non-ulcer subjects, and the potential role of somatostatin and other regulatory peptides in modifying gastrin release and/or gastric acid secretion. Antibodies with precise specificity for limited peptide sequence of gastrin molecules will be used to define gastrin forms in tissues and in the circulation, released in response to stimulation. Region-specific antibodies will be used to identify and discriminate among molecular forms of CCK and gastrin.