Alcohol-induced stimulation of phospholipase C in human platelets requires G-protein activation.
Alcohol-induced stimulation of phospholipase C in human platelets requires G-protein activation.
复制标题
酒精诱导的人血小板磷脂酶 C 的刺激需要 G 蛋白激活。
DOI：
10.1042/bj2540147
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Hoek,JB
中科院分区：
文献类型：
--
作者：
Rubin,R;Hoek,JB
在之前的研究中，我们已经证明乙醇会激活完整人血小板中的激素敏感性磷脂酶 C，导致细胞内 Ca2+ 的动员和血小板形状的改变。本研究旨在通过检查乙醇与透化细胞系统中磷脂酶 C 调节的相互作用，进一步定位乙醇的这种作用。在用最低浓度（18 微克/毫升）皂苷透化的血小板中，乙醇本身不会激活磷脂酶 C。然而，乙醇响应不可水解的 GTP 类似物 GTP[S]（鸟苷 5'-γ-硫代]三磷酸）增强了磷脂酶 C 的激活，其效果与用凝血酶观察到的效果相似。乙醇还增强了对氟化物的反应，氟化物直接作用于 G 蛋白。其他短链醇也与 GTP[S] 协同刺激磷脂酶 C。特定醇刺激磷脂酶 C 的能力与其各自的脂溶性直接相关，这由它们的分配系数决定。此外，每种酒精的效力与其引发完整血小板中 Ca2+ 动员和形状变化的能力相关。通过添加较高浓度的皂苷诱导受体-磷脂酶 C 偶联的破坏，可以消除乙醇的这些影响。这些数据表明，乙醇对磷脂酶 C 的激活可能是通过影响涉及 GTP 结合调节蛋白的信号转导复合物中的蛋白质-蛋白质相互作用而发生的。
In previous studies we have demonstrated that ethanol activates hormone-sensitive phospholipase C in intact human platelets, resulting in the mobilization of intracellular Ca2+ and platelet shape change. The present study aims to localize further this effect of ethanol by examining its interaction with the regulation of phospholipase C in a permeabilized cell system. In platelets permeabilized with a minimal concentration (18 micrograms/ml) of saponin, ethanol by itself did not activate phospholipase C. However, ethanol potentiated the activation of phospholipase C in response to the non-hydrolysable GTP analogue GTP[S] (guanosine 5′-[gamma-thio]triphosphate), an effect similar to that observed with thrombin. Ethanol also potentiated the response to fluoride, which acts directly on G-proteins. Other short-chain alcohols also stimulated phospholipase C in a synergistic manner with GTP[S]. The ability of specific alcohols to stimulate phospholipase C was directly related to their respective lipid-solubilities, as determined by their partition coefficients. Moreover, the potencies of each alcohol correlated with their ability to elicit Ca2+ mobilization and shape change in intact platelets. These effects of ethanol were eliminated by a disruption of receptor-phospholipase C coupling induced by the addition of higher concentrations of saponin. These data indicate that the activation of phospholipase C by ethanol may occur by affecting protein-protein interactions in the signal-transduction complex involving GTP-binding regulatory proteins.