The diacylglycerol kinase inhibitor, R59022, enhances the superoxide generation from human neutrophils induced by stimulation of fMet-Leu-Phe, IgG and C3b receptors.
A specific diacylglycerol kinase inhibitor, at a concentration of 10(-5) M, consistently enhanced superoxide generation from human neutrophils stimulated with fMet-Leu-Phe, IgG, heat-aggregated IgG and opsonized zymosan. The concentration-response curve for fMet-Leu-Phe was displaced to the left and the maximum superoxide release was also consistently increased by R59022 whereas the diacylglycerol lipase inhibitor, RHC80267, 10(-5) M, had no significant effect. These results suggest that the diacylglycerol formed after fMet-Leu-Phe stimulation in human neutrophils is metabolized largely by the kinase and not the lipase, which implies that diacylglycerol is not the major source of arachidonate during signal-transduction.
D003512:Cyclohexanones / Q000494:pharmacology; D019852:Diacylglycerol Kinase; D004075:Diglycerides / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008071:Lipoprotein Lipase / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000378:metabolism*; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D011493:Protein Kinase C / Q000378:metabolism; D011744:Pyrimidinones / Q000494:pharmacology*; D011951:Receptors, Complement / Q000502:physiology*; D017463:Receptors, Complement 3b; D011961:Receptors, Fc / Q000502:physiology*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology*
D003512:Cyclohexanones; D004075:Diglycerides; D011744:Pyrimidinones; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D011961:Receptors, Fc; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D013844:Thiazoles; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; C047505:R 59022; D010770:Phosphotransferases; D019852:Diacylglycerol Kinase; D011493:Protein Kinase C; D008071:Lipoprotein Lipase