Eicosapentaenoic Acid Interferes with U46619-Stimulated Formation of Inositol Phosphates in Washed Rabbit Platelets
Eicosapentaenoic Acid Interferes with U46619-Stimulated Formation of Inositol Phosphates in Washed Rabbit Platelets
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二十碳五烯酸干扰 U46619 刺激的洗涤兔血小板中磷酸肌醇的形成
DOI：
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发表时间：
1989
影响因子：
6.7
通讯作者：
J. Mustard
中科院分区：
文献类型：
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作者：
N. Chetty;J. Vickers;R. Kinlough;M. Packham;J. Mustard
摘要二十碳五烯酸（EPA）抑制血小板对聚集剂的反应性。为了研究EPA影响的反应，我们研究了用EPA预孵育阿司匹林处理的兔血小板对TXA 2类似物U46619刺激磷酸肌醇形成的影响。用U46619（0.5 μM）刺激血小板可引起聚集和致密颗粒内容物的轻微释放;用EPA（50 μM）预孵育血小板1 h，然后洗涤以除去未掺入的EPA，可抑制聚集和释放。与EPA（50 μM）孵育1 h未导致血小板磷脂中EPA量的可检测增加。当用[3 H]肌醇预标记血小板时，用U46619刺激未与EPA孵育的对照血小板显著增加了磷酸肌醇的标记。用50 μM EPA预孵育10 n血小板，可部分抑制10和60 s时U46619引起的磷酸肌醇标记增加。由于环加氧酶的活性被阿司匹林阻断，对U46619的磷酸肌醇标记的抑制表明，可能存在信号转导的抑制而血小板磷脂中EPA的量没有可检测的变化，信号转导的变化仅需要膜磷脂的脂肪酸组成的微小变化，或者在与EPA孵育1小时后，磷脂酶C的活化受到与EPA掺入不直接相关的机制的影响。
Summary Eicosapentaenoic acid (EPA) inhibits platelet responsiveness to aggregating agents. To investigate the reactions that are affected by EPA, we examined the effect of preincubating aspirintreated rabbit platelets with EPA on stimulation of inositol phosphate formation in response to the TXA2 analogue U46619. Stimulation of platelets with U46619 (0.5 μM) caused aggregation and slight release of dense granule contents; aggregation and release were inhibited by preincubation of the platelets with EPA (50 μM) for 1 h followed by washing to remove unincorporated EPA. Incubation with EPA (50 μM) 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 mos1tol phosphates. The increases in inositol phosphate labelling due to U46619 at 10 and 60 s were partially inhibited by premcubat10n of the platelets with 50 μM 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.