Kochhar N, Kaul D
Department of Experimental Medicine, P.G.I.M.E.R., Chandigarh, India.
FEBS Lett. 1992 Mar 24;299(1):19-22. doi: 10.1016/0014-5793(92)80090-4.
Incubation of human platelets with cholesterol-poor, cholesterol-normal and cholesterol-rich liposomes revealed that: (i) acquisition or depletion of platelet membrane cholesterol was highly selective; (ii) variation in membrane cholesterol was highly selective. Variation in membrane cholesterol content (cholesterol-to-phospholipid molar ratio from 0.15-1.2) with respect to values found in unmodified normal platelets, was paralleled by the observed changes in amiloride-sensitive cytoplasmic pH, as well as phospholipase A2 activity. However, a decrease in cytoplasmic pH was accompanied by an increase in phospholipase A2 activity; (iii) membrane cholesterol-modulated changes in intra-platelet pH, as well as phospholipase A2 activity, was completely inhibited when platelets were pretreated with quinacrine (a specific phospholipase A2 inhibitor) before exposure to various types of liposomes. Although exposure of platelets (pretreated with amiloride) with various types of liposomes resulted in the inhibition of Na+/H+ exchange it had no noticeable effect upon the observed phospholipase A2 activity. Based upon these results we suggest that membrane cholesterol-modulated phospholipase A2 activity may be the basic mechanism responsible for the nature of Na+/H+ exchanger activity observed in cholesterol-enriched platelets, leading these platelets to a hypersensitized state.
用人血小板与胆固醇含量低、正常及高的脂质体孵育后发现：（i）血小板膜胆固醇的获取或消耗具有高度选择性；（ii）膜胆固醇的变化具有高度选择性。膜胆固醇含量（胆固醇与磷脂的摩尔比从0.15至1.2）相对于未修饰的正常血小板中的值发生变化时，所观察到的对氨氯地平敏感的细胞质pH值以及磷脂酶A2活性的变化与之平行。然而，细胞质pH值的降低伴随着磷脂酶A2活性的增加；（iii）当血小板在暴露于各种类型的脂质体之前用喹吖因（一种特异性磷脂酶A2抑制剂）预处理时，膜胆固醇调节的血小板内pH值变化以及磷脂酶A2活性变化被完全抑制。尽管用氨氯地平预处理的血小板暴露于各种类型的脂质体导致Na⁺/H⁺交换受到抑制，但对所观察到的磷脂酶A2活性没有明显影响。基于这些结果，我们认为膜胆固醇调节的磷脂酶A2活性可能是导致在富含胆固醇的血小板中观察到的Na⁺/H⁺交换器活性性质的基本机制，使这些血小板处于超敏状态。
