A role of diacylglycerol kinase in stimulus-secretion coupling of human platelets. Dissociation of serotonin secretion from Ca2+ mobilization

Abstract

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.