STIMULUS-RESPONSE COUPLING IN PLATELETS

血小板中的刺激反应耦合

• 批准号: 3335416
• 负责人: THOMAS C DETWILER
• 金额: $ 9.68万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-05-01 至 1987-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3335416
• 关键词: antimetabolites; arachidonate; blood tests; high performance liquid chromatography; human tissue; lipid metabolism; phosphatidylinositols; phospholipids; platelet activating factor; platelet aggregation; platelets; radiotracer; respiratory oxygenation; stimulus /response; thin layer chromatography; thromboxanes

This project is aimed at an understanding of the role of the metabolism of arachidonyl phospholipids in stimulus-response coupling in platelets. Intermediates and end products of the "phosphatidyl inositol effect", of phospholipases A2 and C, and of cyclooxygnase and lipoxygenase will be measured. The rationale is that the major barrior to resolution of the cause-effect relationships of phospholipid metabolism/arachidonate oxygenation in the response of platelets to stimuli is in part because these processes are usually measured during the platelet response to the strongest agonists. Much of the metabolism is thus likely to be a consequence of full platelet activation rather than an expression of a regulatory or second messenger role. Furthermore, it is likely that different pathways (e.g. phospholipase A2 vs phospholipase C) will function under different regulatory demands. This will be analyzed by comparing metabolism in response to weak vs strong agonists, in response to weak agonists where aggregation-mediated activation is permitted or inhibited, and in response to agonists in the presence of various metabolic inhibitors. This should permit correlation of different pathways with specific physiological functions. Arachidonyl phospholipid metabolism will be followed by pre-labelling phospholipids with arachidonate, stearate, or glycerol and by measuring incorporation of 32P into phosphatidic acid. Metabolities will be separated by thin-layer chromatography and high performance liquid chromatography.

该项目的目的是了解 血小板中刺激反应耦合中的蛛网膜磷脂。 “磷脂酰肌醇效应”的中间体和最终产物， 磷脂酶A2和C，以及环氧基因酶和Lipoxygogyase的磷酸酶 测量。 理由是解决方案的主要障碍 磷脂代谢/蛛形代谢的因果关系 血小板对刺激的反应中的氧合作用部分是因为 这些过程通常是在血小板响应中对 最强的激动剂。 因此，许多新陈代谢可能是 全血小板激活而不是表达的结果 监管或第二使者角色。 此外，很可能 不同的途径（例如磷脂酶A2与磷脂酶C）将起作用 根据不同的监管要求。 这将通过比较 响应弱激动剂的代谢，以响应弱 允许或抑制聚集介导的激活的激动剂， 并在存在各种代谢的情况下对激动剂 抑制剂。 这应该允许不同的途径与 特定的生理功能。 Arachidonyl磷脂代谢将 接下来是标签前磷脂，磷酸，硬脂酸酯或 甘油并通过测量将32p掺入磷脂酸中。 代谢将通过薄层色谱分离和高 性能液相色谱。