Fuse I, Tai H H
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Kentucky, Lexington 40536-0082.
Biochim Biophys Acta. 1988 Oct 28;972(1):54-9. doi: 10.1016/0167-4889(88)90102-4.
Thrombin stimulated rapid formation of diacylglycerol, inositol 1,4,5-trisphosphate (IP3) and thromboxane B2 (TXB2) in human platelets. Formation of diacylglycerol and IP3 appeared to precede that of TXB2. Activation of protein kinase C by diacylglycerol combining with Ca+2 mobilization by IP3 has been implicated in mediating arachidonate release. However, addition of the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) to platelet suspension did not inhibit thrombin-stimulated arachidonate release and TXB2 synthesis, whereas addition of the Ca+2 antagonist, 3,4,5-trimethoxybenzoic acid 8-(diethylamino) octyl ester (TMB-8) or the calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) abolished arachidonate release. The correlation of IP3 production with arachidonate release on increasing the concentrations of thrombin was further examined. IP3 production reached near maximum at 0.2 U/ml, whereas TXB2 synthesis continued to increase at 1 U/ml. These results suggest that protein kinase C activation may not mediate arachidonate release and that Ca+2 mobilization by IP3 may only partially account for arachidonate release in platelets stimulated with relatively high concentrations of thrombin.
凝血酶可刺激人血小板中快速形成二酰甘油、肌醇1,4,5 -三磷酸（IP3）和血栓素B2（TXB2）。二酰甘油和IP3的形成似乎先于TXB2。二酰甘油激活蛋白激酶C并与IP3介导的Ca+2动员有关，这一过程参与介导花生四烯酸的释放。然而，向血小板悬液中添加蛋白激酶C抑制剂1 -（5 -异喹啉磺酰基）- 2 -甲基哌嗪（H - 7）并不能抑制凝血酶刺激的花生四烯酸释放和TXB2合成，而添加Ca+2拮抗剂3,4,5 -三甲氧基苯甲酸8 -（二乙氨基）辛酯（TMB - 8）或钙调蛋白拮抗剂N -（6 -氨基己基）- 5 -氯- 1 -萘磺酰胺（W - 7）则可消除花生四烯酸的释放。进一步研究了在增加凝血酶浓度时IP3产生与花生四烯酸释放之间的相关性。IP3的产生在0.2 U/ml时接近最大值，而TXB2的合成在凝血酶浓度为1 U/ml时仍继续增加。这些结果表明，蛋白激酶C的激活可能不介导花生四烯酸的释放，并且IP3介导的Ca+2动员可能仅部分解释了在相对高浓度凝血酶刺激的血小板中花生四烯酸的释放。
