title: Diacylglycerol kinase inhibitor R59022 and stimulated neutrophil responses.
abstract: 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.
authors.affiliation: Department of Physiology, University of Connecticut Health Center, Farmington 06032.
authors.forename: J L
authors.initials: JL
authors.lastname: Mege
authors.forename: W
authors.initials: W
authors.lastname: Tao
authors.forename: T F
authors.initials: TF
authors.lastname: Molski
authors.forename: J
authors.initials: J
authors.lastname: Gomez-Cambronero
authors.forename: C K
authors.initials: CK
authors.lastname: Huang
authors.forename: E L
authors.initials: EL
authors.lastname: Becker
authors.forename: R I
authors.initials: RI
authors.lastname: Sha'afi
mesh_terms: 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*
chemical_list: 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