Chetty N, Vickers J D, Kinlough-Rathbone R L, Packham M A, Mustard J F
Department of Pathology, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
Thromb Haemost. 1989 Dec 29;62(4):1116-20.
Eicosapentaenoic acid (EPA) inhibits platelet responsiveness to aggregating agents. To investigate the reactions that are affected by EPA, we examined the effect of preincubating aspirin-treated rabbit platelets with EPA on stimulation of inositol phosphate formation in response to the TXA2 analogue U46619. Stimulation of platelets with U46619 (0.5 microM) caused aggregation and slight release of dense granule contents; aggregation and release were inhibited by preincubation of the platelets with EPA (50 microM) for 1 h followed by washing to remove unincorporated EPA. Incubation with EPA (50 microM) for 1 h did not cause a detectable increase in the amount of EPA in the platelet phospholipids. When platelets were prelabelled with [3H]inositol, stimulation with U46619 of control platelets that had not been incubated with EPA significantly increased the labelling of inositol phosphates. The increases in inositol phosphate labelling due to U46619 at 10 and 60 s were partially inhibited by preincubation of the platelets with 50 microM EPA. Since the activity of cyclo-oxygenase was blocked with aspirin, inhibition of inositol phosphate labelling in response to U46619 indicates either that there may be inhibition of signal transduction without a detectable change in the amount of EPA in platelet phospholipids, that changes in signal transduction require only minute changes in the fatty acid composition of membrane phospholipids, or that after a 1 h incubation with EPA, activation of phospholipase C is affected by a mechanism that is not directly related to incorporation of EPA.
二十碳五烯酸（EPA）可抑制血小板对聚集剂的反应性。为了研究受EPA影响的反应，我们检测了用EPA预孵育阿司匹林处理过的兔血小板后，对血栓素A2类似物U46619刺激下肌醇磷酸形成的影响。用U46619（0.5微摩尔）刺激血小板会导致聚集以及致密颗粒内容物的轻微释放；在用EPA（50微摩尔）将血小板预孵育1小时后洗涤以去除未结合的EPA，聚集和释放受到抑制。用EPA（50微摩尔）孵育1小时并未使血小板磷脂中EPA的含量出现可检测到的增加。当血小板用[3H]肌醇进行预标记时，未用EPA孵育的对照血小板经U46619刺激后，肌醇磷酸的标记显著增加。在10秒和60秒时，U46619导致的肌醇磷酸标记增加被50微摩尔EPA预孵育血小板部分抑制。由于环氧化酶的活性已被阿司匹林阻断，对U46619反应的肌醇磷酸标记受到抑制表明，要么可能存在信号转导的抑制而血小板磷脂中EPA的含量无可检测到的变化，要么信号转导的变化仅需要膜磷脂脂肪酸组成的微小变化，要么在用EPA孵育1小时后，磷脂酶C的激活受到一种与EPA掺入不直接相关的机制的影响。
