The role of the ileo-colonic junction in modulating performance of the gastrointestinal tract has received little attention, though there is much to suggest that this junctional region has important functions. Thus, the capacity of the large bowel to respond normally, by converting chyme to formed stools, is influenced by the quality and quantity of luminal contents arriving in the proximal colon. The general hypothesis is that the distal ileium, ileocolonic sphincter (ICS) and proximal colon act together as a coordinated segment to regulate transit from ileum to colon; moreover, proper functioning of these mechanisms contributes significantly to normal performance of the distal bowel. Reasons for the relative lack of information on the ileocolonic junction include the inaccessability of the region. In the initial funding period of this grant, methods have been developed which allow the ileocolonic junction to be investigated in dog and man. Further methodological approaches are proposed here together with extensions of earlier studies which will address the mechanisms for control of motility and transit in the region. The experiments described here have the following Specific Aims: 1. To utilize an established and well-characterized canine model to evaluate control of ileocecal motility and transit. The roles of neuro-peptides and pharmacologic agents will be examined. 2. To refine methods by which ileocecal motility and transit can be quantified and correlated in man, and to further evaluate the control of ileocecal function in man. 3. To establish the role of disorders of ileocolonic motility in defined syndromes of gastrointestinal disease. The work outlined here should have direct application to the better understanding of several common gastrointestinal diseases; these include malabsorption syndromes, non-specific diarrhea, irritable bowel syndrome, and the postoperative physiology that follows gastrointestinal surgery.
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