ACTIVATION OF PHOSPHOLIPASE-A AND PHOSPHOLIPASE-C IN HUMAN-PLATELETS EXPOSED TO EPINEPHRINE - ROLE OF GLYCOPROTEIN-IIB GLYCOPROTEINS-IIIA AND DUAL ROLE OF EPINEPHRINE
ACTIVATION OF PHOSPHOLIPASE-A AND PHOSPHOLIPASE-C IN HUMAN-PLATELETS EXPOSED TO EPINEPHRINE - ROLE OF GLYCOPROTEIN-IIB GLYCOPROTEINS-IIIA AND DUAL ROLE OF EPINEPHRINE
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DOI：
10.1073/pnas.83.23.9197
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发表时间：
1986-12-01
影响因子：
11.1
通讯作者：
RITTENHOUSE, SE
中科院分区：
文献类型：
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作者：
BANGA, HS;SIMONS, ER;RITTENHOUSE, SE
肾上腺素刺激的人血小板经历磷脂酰肌醇4，5-二磷酸的增强的周转，积累肌醇三磷酸，甘油二酯和磷脂酸，并磷酸化47-kDa蛋白质。所有这些现象表明磷脂酶C的刺激。这些反应被α 2-肾上腺素能受体（育亨宾）、环氧合酶（阿司匹林或吲哚美辛）、磷脂酶A [2-（对戊基肉桂酰基）氨基-4-氯苯甲酸（ONO-RS-082）]、Na+/H+交换[乙基异丙基氨氯吡嗪（EOPA）]、与糖蛋白IIb/IIIa结合的纤维蛋白原（抗体A2 A9）、Ca 2 +/Mg+结合（EDTA）或去除纤维蛋白原的抑制剂完全阻断。肾上腺素引起（i）阿司匹林处理的血小板中酯连接花生四烯酸的周转增加，其受到ONO-RS-082、EDTA、育亨宾或不存在纤维蛋白原的抑制，和（ii）快速细胞质碱化，其受到部分抑制以阻断环氧合酶活性，并完全受到A2 A9或EIPA的抑制。相反，当与亚聚集浓度的前列腺素H2/血栓烷A2类似物[（15 S）-羟基-11 α，9.阿尔法。（环氧甲酰基）前列腺-5，13-二烯酸（U46619）]和肾上腺素，阿司匹林处理的血小板显示磷脂酶C活化的增强，其不受上述抑制剂的影响。我们认为，肾上腺素，在促进暴露的糖蛋白IIb/IIIa网站的纤维蛋白原结合，导致细胞质碱化，这与当地的变化，在Ca 2+，促进低水平激活磷脂酶A。所产生的游离花生四烯酸转化为环氧合酶产物，其在肾上腺素的增强下激活磷脂酶C。这进一步增强了最初的刺激反应。
Human platelets stimulated by epinephrine undergo enhanced turnover of phosphatidylinositol 4,5-bisphosphate, accumulate inositol triphosphate, diacylglycerol, and phosphatidic acid, and phosphorylate a 47-kDa protein. All of these phenomena indicate stimulation of phospholipase C. These responses are blocked completely by inhibitors of .alpha.2-adrenergic receptors (yohimbine), cyclooxygenase (aspirin or indomethacin), phospholipase A [2-(p-amylcinnamoyl)amino-4-chlorobenzoic acid (ONO-RS-082)], Na+/H+ exchange [ethylisopropylamiloride (EOPA)], fibrinogen binding to glycoprotein IIb/IIIa (antibody A2A9), Ca2+/Mg+ binding (EDTA), or removal of fibrinogen. Epinephrine evokes (i) an increased turnover of ester-linked arachidonic acid in aspirin-treated platelets that is inhibited by ONO-RS-082, EDTA, yohimbine, or the absence of fibrinogen and (ii) a rapid cytoplasmic alkalinization that is inhibited partially to blockage of cyclooxygenase activity and completely by A2A9 or EIPA. In contrast, when incubated with subaggregatory concentrations of the prostaglandin H2/thromboxane A2 analogue [(15S)-hydroxyl-11.alpha.,9.alpha.-(epoxymethano)prosta-5,13-dienoic acid (U46619)] and epinephrine, aspirin-treated platelets show a potentiation of phosholipase C activation that is unaffected by the above inhibitors. We propose that epinephrine, in promoting exposure of glycoprotein IIb/IIIa sites for fibrinogen binding, leads to a cytoplasmic alkalinization, which, in conjunction with local shifts in Ca2+, promotes low-level activation of phospholipase A. The resulting free arachidonic acid is converted to cyclooxygenase products, which, potentiated by epinephrine, activate phospholipase C. This furhter ampiflies the initial stimulatory response.