Previous studies of intestinal adaptation following resection have focused on the marked changes in small bowel morphology and nutrient transport that characterize this phenomenon. Although clinically there is evidence to suggest that there are accompanying alterations in intestinal fluid and electrolyte transport, this has not been examined experimentally in any detail. The hypothesis underlying this application is that, following resection, the adaptation in intestinal fluid and electrolyte transport is of comparable magnitude and physiologic significance and that the mechanisms and magnitude of this response depend on both the segment of bowel examined and on a variety of luminal, systemic, and cellular mediators. To evaluate this, we plan a series of experiments, based on preliminary data employing a rat model of massive small bowel resection, to address the following specific aims: 1. To examine the' effects of adaptation on fluid and electrolyte transport in jejunum, ileum, and colon. 2. To identify the cellular transport mechanisms responsible for this functional change. 3. To begin to determine the molecular basis for this adaptation. 4. To examine the role of luminal contents in this response. 5. To evaluate the role of one specific neuroendocrine mediator, peptide YY, in this alteration in fluid and electrolyte transport. The results of these experiments should have considerable relevance clinically. Not only may they increase our understanding of recovery following intestinal resection but they should also find application to a variety of other clinical problems ranging from ileostomy diarrhea to recovery following small bowel transplantation.
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