Diacylglycerol kinase inhibitor R59022 and stimulated neutrophil responses.
The generation of phosphatidic acid in neutrophils stimulated by the chemotactic factor formylmethionyl-leucyl-phenylalanine (fMet-Leu-Phe) is inhibited by the diacylglycerol kinase inhibitor R59022. Superoxide generation produced by fMet-Leu-Phe, leukotriene B4, platelet-activating factor, or phorbol 12-myristate 13-acetate can be greatly increased in neutrophils pretreated with R59022. The potentiation occurs in the presence or absence of cytochalasin B and is evident in the absence of extracellular calcium. In addition, where the superoxide generated by fMet-Leu-Phe is not inhibited by the protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), the increase by R59022 is diminished by this compound. Unlike cytochalasin B, R59022 does not affect the increase in cytoskeletal actin produced by fMet-Leu-Phe or platelet-activating factor nor does it decrease the basal level. Furthermore, the basal intracellular concentration of free calcium, but not the rise produced by fMet-Leu-Phe or platelet-activating factor, is elevated by R59022. The data presented here suggest that the potentiation by R59022 of the oxidative burst is most likely mediated through protein kinase C.
Mege
J L
JL
Department of Physiology, University of Connecticut Health Center, Farmington 06032.
Tao
W
W
Molski
T F
TF
Gomez-Cambronero
J
J
Huang
C K
CK
Becker
E L
EL
Sha'afi
R I
RI
D000818:Animals; D019852:Diacylglycerol Kinase; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010712:Phosphatidic Acids / Q000378:metabolism; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D011494:Protein Kinases / Q000378:metabolism; D011744:Pyrimidinones / Q000494:pharmacology*; D011817:Rabbits; D013268:Stimulation, Chemical; D013481:Superoxides / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*
D010712:Phosphatidic Acids; D011744:Pyrimidinones; D013844:Thiazoles; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; C047505:R 59022; D010770:Phosphotransferases; D011494:Protein Kinases; D019852:Diacylglycerol Kinase