Tohmatsu T, Nakashima S, Hattori H, Suganuma A, Nozawa Y
Department of Biochemistry, Gifu University School of Medicine, Japan.
Thromb Res. 1987 Jul 1;47(1):25-35. doi: 10.1016/0049-3848(87)90237-4.
The addition of diacylglycerol kinase inhibitor, R 59 022 (6-[2-[4-[(4-fluorophenyl)phenylmethylene]-1-piperidinyl]-7-methyl - 5H-thiazolo[3,2-alpha]pyrimidin-5-one) resulted in a marked accumulation of diacylglycerol in thrombin-stimulated platelets. Release of arachidonic acid induced by thrombin was not affected by the inhibitor. In intact platelets, the conversion of exogenously added 1-oleoyl-2-acetylglycerol to 1-oleoyl-2-acetylphosphatidic acid also was inhibited by the inhibitor. We further investigated the effects of the inhibitor on serotonin secretion and Ca2+ mobilization in thrombin-activated platelets. R 59 022 potentiated serotonin secretion induced by thrombin or 1-oleoyl-2-acetylglycerol. On the other hand, the thrombin-induced increase in cytosolic free Ca2+ concentration measured with aequorin or Quin2 was found to be depressed by R 59 022. These results indicate that diacylglycerol kinase has an important role in regulation of serotonin secretion and that Ca2+ mobilization may not be tightly coupled to serotonin secretion.
添加二酰基甘油激酶抑制剂R 59 022（6-[2-[4-[(4-氟苯基)苯基亚甲基]-1-哌啶基]-7-甲基-5H-噻唑并[3,2-α]嘧啶-5-酮）导致凝血酶刺激的血小板中二酰基甘油显著积累。凝血酶诱导的花生四烯酸释放不受该抑制剂影响。在完整血小板中，该抑制剂也抑制外源性添加的1-油酰基-2-乙酰甘油向1-油酰基-2-乙酰磷脂酸的转化。我们进一步研究了该抑制剂对凝血酶激活的血小板中5-羟色胺分泌和Ca2+动员的影响。R 59 022增强了凝血酶或1-油酰基-2-乙酰甘油诱导的5-羟色胺分泌。另一方面，发现用发光蛋白或喹啉2测量的凝血酶诱导的胞质游离Ca2+浓度升高被R 59 022抑制。这些结果表明二酰基甘油激酶在5-羟色胺分泌调节中起重要作用，并且Ca2+动员可能与5-羟色胺分泌没有紧密联系。
