MECHANISMS OF AGEPC ACTION ON VASCULAR ENDOTHELIUM

拟议的研究计划将集中在行动的乙酰甘油 乙醚磷酸胆碱（AGEPC，血小板活化因子），一种有效的 血管活性/炎症介质，对血管中钙稳态的影响 内皮细胞 AGEPC特异性作用的生化和细胞机制 对钙运动（45 Ca 2+通量）和细胞溶质游离钙 浓度（quin 2，钙敏感性荧光染料）进行研究 在从不同血管类型分离的培养内皮细胞中， 物种 具体目标包括：（1）确定时间和 AGEPC诱导的内皮细胞变化的浓度依赖性模式 钙稳态; 2）确定细胞的来源和汇 钙参与AGEPC的作用; 3）表征激动剂诱导的 AGEPC效应的脱敏和AGEPC的潜在相互作用 和内皮钙中的其他血管活性/炎症物质 内稳态; 4）确定不同钙拮抗剂在 该系统;和5）检测环核苷酸（环AMP， 环GMP）和环氧合酶产物（前列环素）在内皮细胞 钙稳态 这些研究应提供新的信息， AGEPC作用于血管内皮的细胞机制， 与急性和慢性炎症有关。 此外，这些研究可能 也提供了新的见解，改变内皮钙的作用， 在更复杂的血管疾病的发病机制中的稳态，例如 血栓形成和动脉粥样硬化。

The proposed research plan will focus on the action of acetyl glyceryl ether phosphorylcholine (AGEPC, platelet activating factor), a potent vasoactive/inflammatory mediator, on calcium homeostasis in vascular endothelium. Biochemical and cellular mechanisms of AGEPC-specific effects on calcium movements (45Ca2+ flux) and on cytosolic free calcium concentration (quin 2, calcium-sensitive fluorescent dye) will be studied in cultured endothelial cells isolated from different vessel types and species. Specific aims include: 1) defining the temporal- and concentration-dependent patterns of AGEPC-induced changes in endothelial calcium homeostasis; 2) identifying the sources and sinks of cellular calcium involved in the action of AGEPC; 3) characterizing agonist-induced desensitization of AGEPC effects and the potential interactions of AGEPC and other vasoactive/inflammatory substances in endothelial calcium homeostasis; 4) defining the effects of different calcium antagonists in this system; and 5) examining the role of cyclic nucleotides (cyclic AMP, cyclic GMP) and cyclooxygenase products (prostacyclin) in endothelial calcium homeostasis. These studies should provide new information on the cellular mechanisms of AGEPC action on vascular endothelium, a process relevant to acute and chronic inflammation. In addition, these studies may also provide new insights into the role of altered endothelial calcium homeostasis in the pathogenesis of more complex vascular diseases, such as thrombosis and atherosclerosis.