EXTRINSIC CONTROL OF GASTROINTESTINAL MOTILITY

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The long term objective is to understand how the prevertebral ganglia regulate/modulate colonic, small intestinal and gastric motility. Toward this objective four major areas of study are planned. In the first, experiments are designed to determine the functional role of substance P, vasoactive intestinal polypeptide, the enkephalin and bombesin in the regulation of colonic motility. In the second, the pattern and nature of synaptic input to and the electrophysiological properties of intramural ganglion cells will be determined with the view that these parafascicular ganglion distribute central commands to the myenteric plexus and thereby play a role in influencing or controlling gastric motility. In the third area, sympathetic regulation of gastric and intestinal motility will be addressed by identifying the precise arrangement between preganglionic fibers arising from the thoraco-lumbar spinal cord and ganglion cells in the celiac ganglia. In the final area, experiments are designed to delineate the wiring of the abdominal prevertebral ganglia by determining the nature and extent of intra- and inter-ganglionic connections between ganglion cells in the same and adjacent ganglia and by determining the topographical (spatial) arrangement of ganglion cells in the prevertebral ganglia which innervate the stomach and different functional regions of the small intestine. The methods of approach will involve immunological techniques including radioimmunoassay and immunopharmacological methods, measurement of intraluminal pressure in segments of the gastrointestinal tract, intracellular recordings from individual ganglion cells and morphological techniques using the horseradish peroxidase method of marking neurons. Both in vitro and in vivo experiments are planned. Guinea pigs and cats will be used for studies on the pevertebral ganglia whereas opossum will be used for studies on intramural ganglion cells of the stomach. These studies may be particularly relevant to disturbances in gastrointestinal motility including ileus or adynamic bowel, pseudo-obstruction, gastric atonia and autonomic dysfunction affecting gastric and intestinal motility. These studies may also shed some light on the possible neural peptidergic basis for an association between visceral pain and gastrointestinal motor abnormalities.