AGEPC--A POTENT LIPID BIOCHEMICAL MEDIATOR IN LIVER

这项调查的主要目标将是探索 强效脂质生化介体的生化模式(S)， 肝脏中的乙酰甘油醚磷酰胆碱(AGEPC)。这种化合物有 早先被确认为“血小板活化因子”，在 对兔的全身性过敏反应，现在被认为是最 与急性过敏和炎症反应有关的强有力的介体。 最近，我们的实验室观察到，这种化合物具有 对肌醇磷脂代谢和葡萄糖释放的深刻影响 肝脏制剂。本研究将采用的实验方法 最好用以下具体目标来表达： 一、从酶水平表征AGEPC的刺激作用 关于肝脏糖原分解。 II.探讨AGEPC刺激血管紧张素转换酶的作用机制 肝脏糖异生。 III.评价AGEPC对小鼠代谢的影响 肝脏和细胞内钙离子通量的变化。 IV.检查和比较AGEPC和其他糖原分解剂的效果 激素对磷脂酰肌醇等磷脂代谢的影响 肝细胞。 研究AGEPC在肝脏中的代谢去向。 六、确定糖原分解激素是否添加到 肝脏导致AGEPC或密切相关的衍生物的产生(S)。 研究肝细胞膜AGEPC受体的特性。 这个项目应该提供对这一机制的新见解 非同寻常的磷脂及其类似物对一种 非炎性细胞，在这种情况下，并有望发展为 探讨AGEPC在其他组织和组织中的作用模式 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.