YALE UNIVERSITY CUSHING/WHITNEY MEDICAL LIBRARY Digitized by the Internet Archive in 2017 with funding from Arcadia Fund https://archive.org/details/counterregulatioOOferz COUNTER-REGULATION OF ILEAL MOTILITY IN RABBIT SMALL INTESTINE A Thesis Submitted to the Yale University School of Medicine in partial fulfillment of the requirements for the Degree of Doctor of Medicine by Stephen John Ferzoco . I ( 4 1993 fKe^S' - b r//3 t? ii (tlb? KUtoa 06-93 FERZOCO, SJ 2 - - COUNTER-REGULATION OF ILEAL MOTILITY IN RABBIT SMALL INTESTINE. Stephen J. Ferzoco. Department of Surgery, Yale University School of Medicine, New Haven, CT. Disorders of intestinal motility continue to plague surgeons of the twentieth century. Unfortunately, the regulation of intestinal motility remains incompletely understood. Utilizing the isolated whole organ perfusion system, segments of rabbit terminal ileum were infused with variety of known gastrointestinal hormones, peptides and neurotransmitters. In the first series of experiments, prokinetic agents such as carbachol (an acetylcholine analogue), cholecystokinin, motilin and were tested. All three agents caused a concentration-dependent increase in measured motor activity. In the second series of experiments, agents which increase intracellular levels of cAMP, vasoactive intestinal peptide (VIP), forskolin and norepinephrine, were tested against prokinetic-stimulated segments of ileum. All three agents caused a concentration- dependent inhibition of motility. In the third series of experiments, neuropeptide Y (NPY) and peptide YY (PYY), agents which block intracellular cAMP, reversed the inhibitory action of VIP. In the final series of experiments, various NPY/PYY analogues with specific Y receptor affinity were tested. The Yx receptor analogue . ■*