AGEPC--A POTENT LIPID BIOCHEMICAL MEDIATOR IN LIVER

本次调查的主要目的是探索 有效脂质生化介质的生化作用模式， 乙酰甘油醚磷酸胆碱，AGEPC。 该化合物具有 以前被确定为“血小板活化因子”， 全身过敏反应，现在被认为是最重要的 涉及急性过敏和炎症反应的强效介质。 最近，我们的实验室观察到，这种化合物具有 对磷脂酰肌醇代谢和葡萄糖释放的显著活性， 肝脏制剂。 本研究采用的实验方法 最好体现在以下具体目标中： I.在酶水平表征AGEPC的刺激作用 肝糖原分解 二.探讨AGEPC刺激细胞凋亡的机制， 肝再生 三.评价AGEPC的代谢效应与 肝脏和细胞钙离子流的改变。 四.检测并比较AGEPC和其他糖原分解剂的作用， 激素对磷脂酰肌醇和其他磷脂代谢的影响 肝细胞 诉研究AGEPC在肝脏中的代谢归宿。 六.为了确定是否加入糖原分解激素， 肝脏导致AGEPC或密切相关的衍生物的产生。 七.表征肝细胞膜上AGEPC的受体。 该项目应提供新的见解的机制， 不寻常的磷脂及其类似物发挥其活性， 在这种情况下，它是一种非炎症细胞， 研究AGEPC在其他组织中的作用模式的模型， 细胞

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.