The goal of this project is to define the role of endogeneous prostaglandins in the control of gastric and intestinal motility. General questions under investigation will be: 1) Which prostaglandins are synthesized in physiologically significant concentrations? 2) What stimuli alter prostaglandin biosynthesis, 3) what are the mechanical consequences of endogeneous prostaglandins, 4) what are the electrophysiological mechanisms of the motor effects of prostaglandins. Prostaglandins probably function as local regulatory compounds, which means their synthesis, effect and deactivation must all occur locally, within the tissue. Therefore, the questions above will be studied with an in vitro, canine smooth muscle preparation. This proposal is unique because it will combine several well-known techniques to produce a unified picture of prostaglandin physiology. Microsomal preparations of muscle will be used to determine the types of prostaglandins the muscles are capable of producing. Radioimmunoassay (RIA) of muscle extracts will be used to measure basal prostaglandin levels and quantitate relative changes in prostaglandin concentration in response to various stimuli. Mechanical and intracellular electrical measurements will be made to isolate common aspects of stimuli which enhance prostaglandin synthesis, to determine the influence of endogenous prostaglandins and electrical and mechanical activities, and to determine the mechanism of the electrical and mechanical effects of prostaglandins. In parallel experiments normal and malfunctioning human gastric and intestinal muscles removed during corrective GI surgery will be studied. The techniques above will be applied in these studies to test the hypothesis that some pseudo-obstruction disorders are related to an over-abundance of endogenous prostaglandin.
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