INVESTIGATIONS OF PLATELET MEMBRANE MODULATION

这个实验室最近的研究已经证实了 确保不可逆的血小板聚集的新机制 独立于ADP分泌、前列腺素合成或 血小板活化因子(PAF)。新的机制，称为膜 调节与血小板表面有关，通过阿尔法调节 肾上腺素能受体，并受肾上腺素刺激。血小板 对各种聚集剂产生的耐火材料可以恢复到 通过激活膜的机制而达到的正常敏感性状态 调制。这包括体内或体内使用阿司匹林治疗的血小板。 阿司匹林治疗的血小板将作为主要的模型 在这次调查期间要进行的研究。目的 本研究旨在探讨和明确血小板膜的作用机制。 详细介绍了调制方式。有可能新一代的产品 阿司匹林治疗后血小板脂氧合酶途径、内源性升高 循环GMP水平，纤维蛋白原受体暴露，动员 钙，膜相关蛋白的磷酸化或还原 血红素蛋白可能抑制肾上腺素引起的膜激活 阿司匹林治疗中膜敏感度的调制与校正 细胞。适当的生化、生理和形态方法 将被用来详细研究每一种可能性。 这些具体目标的实现将揭示根本 血小板调节的潜在机制。获得的能力 这一新发现的调控机制的药理学控制 血小板膜活化，不可逆保护 前列腺素合成缺失时难治性细胞的聚集 或ADP分泌可能提供一种新的治疗和治疗方法。 预防血栓性疾病。

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.