SUPPRESSIVE EFFECT OF BISCOCLAURINE ALKALOIDS ON AGONIST-INDUCED ACTIVATION OF PHOSPHOLIPASE-A2 IN RABBIT PLATELETS
SUPPRESSIVE EFFECT OF BISCOCLAURINE ALKALOIDS ON AGONIST-INDUCED ACTIVATION OF PHOSPHOLIPASE-A2 IN RABBIT PLATELETS
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DOI：
10.1016/0006-2952(91)90539-h
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发表时间：
1991-02-01
影响因子：
5.8
通讯作者：
FUJII, T
中科院分区：
文献类型：
--
作者：
HASHIZUME, T;YAMAGUCHI, H;FUJII, T
研究了双苄基异喹啉生物碱对兔血小板信号转导系统中磷脂酶A2和C活化的影响。异粉防己碱、头孢蒽醌和小檗碱抑制胶原诱导的聚集，但不抑制凝血酶和花生四烯酸等其他刺激，而粉防己碱同样抑制这些激动剂的聚集。所有这四种生物碱都抑制胶原蛋白或凝血酶对花生四烯酸的释放，但不抑制二酰基甘油的形成和凝血酶或花生四烯酸对细胞质Ca2+浓度的增加。在皂素渗透的血小板中，它们也抑制了GTPgammaS和Ca2+的添加诱导的花生四烯酸的释放，而单独添加Ca2+诱导的释放并没有被它们阻止。这些数据表明，异粉防己碱、头孢酞氨酸和小檗碱具有相当特异性的抑制磷脂酶A2激活的效力，而不是通过直接抑制酶或干扰配体-受体相互作用的机制。它们似乎至少在一定程度上对血小板信号转导系统中gtp结合蛋白-磷脂酶A2复合体产生影响。相反，粉防己碱除了抑制磷脂酶A2的激活外，似乎还抑制激动剂诱导的信号转导系统中细胞质游离Ca2+浓度增加的一个步骤。
The effect of biscoclaurine (bisbenzylisoquinoline) alkaloids on phospholipase A2 and C activation in signal transduction system of rabbit platelet was studied. Isotetrandrine, cepharanthine and berbamine inhibited the aggregation induced by collagen but not by other stimuli such as thrombin and arachidonic acid, while tetrandrine equally inhibited the aggregation by any of these agonists. All these four alkaloids suppressed arachidonic acid liberation in response to collagen or thrombin, but not diacylglycerol formation and increase in cytoplasmic Ca2+ concentration in response to thrombin or arachidonic acid. In saponin-permeabilized platelets, they also suppressed arachidonic acid liberation induced by an addition of both GTPgammaS and Ca2+, whereas the liberation induced by an addition of Ca2+ alone was not prevented by them. These data suggest that isotetrandrine, cepharanthine and berbamine have a rather specific potency to suppress the phospholipase A2 activation by a mechanism other than direct inhibition of the enzyme or interference with the ligand-receptor interaction. They seem, at least in part, to exert the effect on the GTP-binding protein-phospholipase A2 complex in the platelet signal transduction system. In contrast, tetrandrine appears to inhibit a step following an increase in cytosolic free Ca2+ concentration in the agonist-induced signal transduction system, in addition to suppressing the phospholipase A2 activation.