The overall objective of this research proposal is to elucidate the myogenic, neural and peptidergic control of colonic motility in health and disease. During the past few years we have defined the migrating and non-migrating motor complexes and their myoelectric correlates in the dog colon (1,2). We have also defined the short and long duration contractions in the dog and human colon (2-6). Our objectives now are to determine 1) the extrinsic and intrinsic neural control of initiation and migration of colonic motor complexes, 2) the effects of certain physiological stimuli such as high and low fiber diets on the organization of colonic motor complexes, 3) the effects of fluid load and direct administration of laxatives into the colon on colonic motor activity, and 4) the site of action of a few of the relevent peptides in the enteric nervous system and their effects on colonic motor activity. The experiments will be done on conscious and anesthetized dogs. Motor and myoelectric activities will be recorded by surgically implanted strain gage transducers and bipolar electrodes under general anesthesia. The role of extrinsic nerves in the control of colonic motor complexes will be determined by the technique of nerve section and of intrinsic nerves by multiple myotomies. The effects of fluid load and laxatives on colonic motor activity will be studied in the intact colon and in isolated colonic loops. Fluids and laxatives will be infused into the lumen of the colon through indwelling silastic catheters. The coupling between electrical and contractile activities and the peripheral effects of peptides will be studied by close-intraarterial injections of these substances in short segments of the colon. The data will be analysed by computer and visual methods. Our long term goal is to apply the knowledge and understanding obtained from animal experiments to the study of human colonic motor function in health and in various pathological states such as irritable bowel syndrome, idiopathic intestinal pseudo-obstruction and diverticular disease. An insight into the normal functioning of the myogenic, neural and chemical (including peptides) control mechanisms in health and colonic motor disorders is essential to propose appropriate pharmacologic, therapeutic and surgical measures to normalize colonic motor function in disease or to provide a symptomatic relief.
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