INVESTIGATIONS OF PLATELET MEMBRANE MODULATION

血小板膜调节的研究

• 批准号: 3341272
• 负责人: GUNDU H RAO
• 金额: $ 7.49万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1987-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3341272
• 关键词: adenosine diphosphate; arachidonate; aspirin; calcium; chemical binding; cyclic GMP; eicosanoid metabolism; epinephrine; fatty acid biosynthesis; fibrinogen; gel filtration chromatography; hemoprotein; human tissue; ionophores; lipoxygenase; membrane activity; membrane permeability; membrane structure; phosphorylation; platelet activating factor; platelet aggregation; radioassay

Recent investigations in this laboratory have established existence of a novel mechanism capable of securing irreversible platelet aggregation independent of ADP secretion, prostaglandin synthesis or the generation of platelet activating factor (PAF). The new mechanism, termed membrane modulation, is associated with the platelet surface, mediated through Alpha adrenergic receptors and stimulated by exposure to epinephrine. Platelets rendered refractory to a variety of aggregating agents can be restored to a normal state of sensitivity through activation of the mechanism of membrane modulation. This includes platelets treated with aspirin in vivo or in vitro, and the aspirin treated platelet will serve as a principal model for the studies to be carried out during this investigation. The purpose of this proposal is to explore and define the mechanism of platelet membrane modulation in detail. It is possible that generation of products of the lipoxygenase pathway in aspirin treated platelets, elevation of endogenous levels of cyclic GMP, exposure of fibrinogen receptors, mobilization of calcium, phosphorylation of membrane associated proteins or reduction of heme proteins may underly the epinephrine induced activation of membrane modulation and correction of membrane sensitivity in aspirin treated cells. Appropriate biochemical, physiological and morphological methods will be used to study each of these possibilities in detail. Accomplishment of these specific aims will reveal the fundamental mechanisms underlying the platelet modulation. The ability to gain pharmacological control of this newly discovered mechanism regulating platelet membrane activation and capable of securing irreversible aggregation of refractory cells in the absence of prostaglandin synthesis or ADP secretion may provide a new approach to the management and prevention of thrombotic disease.

该实验室最近的研究表明， 能够确保不可逆血小板聚集的新机制 不依赖于ADP分泌、前列腺素合成或 血小板活化因子（PAF）。 这种新的机制被称为膜 调节，与血小板表面有关，通过α-淀粉酶介导。 肾上腺素能受体并通过暴露于肾上腺素而刺激。 血小板 使其对各种聚集剂难治， 通过激活膜机制的正常敏感状态 调变 这包括在体内或体内用阿司匹林处理的血小板。 体外，阿司匹林处理的血小板将作为主要模型， 在本次调查期间进行的研究。 的目的 本研究旨在探讨和明确血小板膜的形成机制， 调制细节 可能的是， 阿司匹林处理的血小板中的脂氧合酶途径，内源性 环GMP水平，纤维蛋白原受体暴露， 钙、膜相关蛋白的磷酸化或 血红素蛋白可能是肾上腺素引起的膜活化的基础 阿司匹林治疗中膜敏感性的调节和校正 细胞 适当的生物化学、生理学和形态学方法 将被用来详细研究这些可能性。 这些具体目标的实现将揭示基本的 血小板调节的潜在机制。 获得的能力 这种新发现的调节机制的药理学控制 血小板膜活化，并能够确保不可逆的 在缺乏前列腺素合成的情况下，不应细胞聚集 或ADP分泌可能提供一种新的方法来管理， 预防血栓性疾病。