AGEPC--A POTENT LIPID BIOCHEMICAL MEDIATOR IN LIVER

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The major objective of this investigation will be to explore the biochemical mode(s) of action of the potent lipid biochemical mediator, acetylglyceryletherphosphorylcholine, AGEPC, in liver. This compound has been identified previously as "platelet activating factor", released during systemic anaphylaxis in rabbits and now recognized as one of the most potent mediators implicated in acute allergic and inflammatory reactions. Recently our laboratories have observed that this compound exerts a profound activity on phosphoinositide metabolism and glucose release in liver preparations. The experimental approach to be employed in this study is best expressed in the following specific aims: I. To characterize at the enzymatic level the stimulatory effect of AGEPC on hepatic glygcogenolysis. II. To investigate the mechanism of the stimulatory effect of AGEPC on hepatic gluconeogenesis. III. To evaluate the relationship between the metabolic effects of AGEPC in the liver and alterations in the cellular calcium ion fluxes. IV. To examine and to compare the effects of AGEPC and other glycogenolytic hormones on the metabolism of phosphoinositides and other phospholipids in hepatocytes. V. To investigate the metabolic fate of AGEPC in the liver. VI. To determin whether the addition of glycogenolytic hormones to the liver results in the production of AGEPC or closely related derivative(s). VII. To characterize the receptor for AGEPC on hepatic cellular membranes. This project should provide new insights into the mechanism by which this unusual phospholipid and its analogues exert their activity towards a non-inflammatory cell, in this instance, and hopefully will develop as a model for inquiry into the mode of action of AGEPC in other tissues and cells.