Hashizume T, Yamaguchi H, Sato T, Fujii T
Department of Biochemistry, Kyoto Pharmaceutical University, Japan.
Biochem Pharmacol. 1991 Feb 1;41(3):419-23. doi: 10.1016/0006-2952(91)90539-h.
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 GTP gamma S 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.
研究了蝙蝠葛碱（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激活的影响。异粉防己碱、千金藤素和小檗胺抑制胶原蛋白诱导的聚集，但不抑制凝血酶和花生四烯酸等其他刺激物诱导的聚集，而粉防己碱对这些激动剂中的任何一种诱导的聚集均有同等程度的抑制作用。这四种生物碱均抑制胶原蛋白或凝血酶诱导的花生四烯酸释放，但不抑制凝血酶或花生四烯酸诱导的二酰甘油形成及细胞质Ca2+浓度升高。在皂苷通透的血小板中，它们还抑制同时添加GTPγS和Ca2+诱导的花生四烯酸释放，而单独添加Ca2+诱导的释放则不受其抑制。这些数据表明，异粉防己碱、千金藤素和小檗胺具有相当特异的抑制磷脂酶A2激活的能力，其机制并非直接抑制该酶或干扰配体-受体相互作用。它们似乎至少部分地对血小板信号转导系统中的GTP结合蛋白-磷脂酶A2复合物发挥作用。相比之下，粉防己碱除了抑制磷脂酶A2激活外，似乎还在激动剂诱导的信号转导系统中抑制胞质游离Ca2+浓度升高后的一个步骤。
