A role of diacylglycerol kinase in stimulus-secretion coupling of human platelets. Dissociation of serotonin secretion from Ca2+ mobilization.
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.
Tohmatsu
T
T
Department of Biochemistry, Gifu University School of Medicine, Japan.
Nakashima
S
S
Hattori
H
H
Suganuma
A
A
Nozawa
Y
Y
D000634:Aminoquinolines; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D019852:Diacylglycerol Kinase; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D010770:Phosphotransferases / Q000037:antagonists & inhibitors / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects; D011744:Pyrimidinones / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D000634:Aminoquinolines; D001095:Arachidonic Acids; D004791:Enzyme Inhibitors; D011744:Pyrimidinones; D013844:Thiazoles; D016718:Arachidonic Acid; D012701:Serotonin; C047505:R 59022; D010770:Phosphotransferases; D019852:Diacylglycerol Kinase; D013917:Thrombin; C035739:Quin2; D002118:Calcium