Support is requested to investigate the regulation and adaptation of gastrointestinal function. Support is requested for six projects, three scientific cores, and an administrative core, all of which will benefit from the interactions of the project personnel and the support provided by the cores. Project 1 will examine the role of food in the gut in the regulation of gastrointestinal adaptation as related to growth and function. This will be studied in models of normal gastric development, intestinal resection and by-pass and the presentation of specific nutrients to the gut. Project 2 will describe the changes that take place in intestinal smooth muscle during adaptation and determine possible mechanisms responsible. The physical and biochemical properties of smooth muscle will be studied following intestinal bypass and related to changes in both local and systemic factors. Project 3 will examine in dynamic terms how the intrinsic propulsive ability of various intestinal regions develops and adapts to resection, by-pass, obstruction and denervation. Project 4 will make use of ion-selective electrodes and patch-clamp techniques to gain insight into the regulation of K+ and Na+ entrance and exit across epithelial cells. Project 5 will explore the mechanisms whereby bile acids induce active secretion in the colon, taking advantage of the finding that this induction is absent from the colon of the newborn rabbit. Project 6 will employ a variety of physiological systems and immunological techniques to test the hypothesis that rapid, immune rejection of T. spiralis is an adaptive response effected through physiological alterations in the small intestinal epithelium. These projects will be supported by three scientific cores: (A) Animal Surgery and Maintenance, (B) Morphology, (C) Computational and an administrative core (D) The studies outlined are basic in nature; however, the information derived will be applicable to a variety of normal functions and clinical conditions. These include gastrointestinal development, and the effects of dietary constituents on the G.I. tract, diarrhea resulting from alterations in motility and transport processes, ulcers, and conditions such as short bowel syndrome, intestinal obstruction, and parasitism.
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