PAF STIMULATED PHOSPHOINOSITIDE TURNOVER IN PLATELETS

PAF 刺激血小板中的磷酸肌醇周转

• 批准号: 3233434
• 负责人: Shivendra D Shukla
• 金额: $ 8.16万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-01-01 至 1988-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3233434
• 关键词: high performance liquid chromatography; human tissue; inositol; lipid metabolism; phosphatidylinositols; phospholipase C; platelet activating factor; platelets; serotonin

Platelet activating factor (PAF), a phospholipid, has an assigned structure of 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (AGEPC). It affects the function of several cells and tissues. The most pronounced effect of this compound is on platelets, a blood cell with important role in cardiovascular processes. AGEPC stimulates platelets and also causes rapid turnover of polyphosphoinositides (PPI). The theme is to elucidate the 'mechanism" and "importance' of AGEPC stimulated PPI turnover in platelets. Based on new experimental findings it is our hypothesis that phosphoinositide phosphodiesterase (phospholipase C) plays a key role in AGEPC stimulated activation of platelets. The following experimental strategies will form the basis of this project [I] To establish characteristics of the key enzyme (phospholipase C) involved in PPI turnover; its regulation by selected agents. [II] Relationship between PPI turnover and AGEPC receptor; Is AGEPC receptor a PPI phosphodiesterase? [III] Study of possible link between PPI turnover and platelet refractoriness (desensitization) to AGEPC. [IV] Study of AGEPC stimulated PPI turnover in platelets with in situ manipulated levels of PPI; or in platelets from pathophysiological states. AGEPC is emerging as a potent mediator (autacoid). PPI turnover is drawing support for being a cell signalling event. How this signal-mechanism is involved in biochemical mode of action of this new mediator (AGEPC) is therefore an important issue. This will be explored using platelets as a model cell.

血小板活化因子（PAF）是一种磷脂，具有指定的结构 1-O-烷基-2-乙酰基-sn-甘油基-3-磷酸胆碱（AGEPC）。 它影响 几种细胞和组织的功能。 最明显的效果 这种化合物存在于血小板上，血小板是一种在 心血管过程 AGEPC刺激血小板，也引起快速 聚磷酸肌醇（PPI）的周转。 主题是阐明 AGEPC刺激PPI周转的“机制”和“重要性” 血小板 根据新的实验发现，我们的假设是， 磷酸肌醇磷酸二酯酶（磷脂酶C）在 AGEPC刺激血小板活化。 以下实验策略将构成本项目的基础 [I]确定关键酶磷脂酶C的特性 参与生产者价格指数的交易;由选定的代理人进行监管。 [II]PPI转换与AGEPC受体的关系 受体a PPI磷酸二酯酶？ [III]PPI转换与血小板之间可能联系的研究 对AGEPC不敏感（脱敏）。 [IV]AGEPC促进血小板PPI周转的原位研究 操纵PPI水平;或在病理生理状态下的血小板中。 AGEPC正在成为一种强有力的介质（autacoid）。 PPI成交量正在绘制 支持作为小区信令事件。 这种信号机制是如何 参与这种新介质（AGEPC）的生化作用模式的是 因此是一个重要的问题。 这将使用血小板作为 模型细胞