Diacylglycerol kinase inhibitors R59022 and dioctanoylethylene glycol potentiate the respiratory burst of neutrophils by raising cytosolic Ca2+.
The diacylglycerol kinase inhibitors, R59022 and dioctanoylethylene glycol (diC8-eg), potentiate stimulation of the respiratory burst by the chemotactic tripeptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) in human neutrophils. However, in contrast to the potentiation observed in intact cells, neither R59022 nor diC8-eg enhanced the effect of fMLP on O2 consumption in electropermeabilized neutrophils, under conditions where cytosolic [Ca2+] was held constant using EGTA. In unstimulated, intact cells treatment with the diacylglycerol kinase inhibitors elicited an increase in cytosolic Ca2+ ([Ca2+]i). The results suggest that enhancement of the respiratory burst by diC8-eg and R59022 is mediated by a rise in [Ca2+]i, rather than by inhibition of diacylglycerol kinase.
Nasmith
P
P
Division of Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
Grinstein
S
S
D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability; D003600:Cytosol / Q000378:metabolism; D019852:Diacylglycerol Kinase; D004357:Drug Synergism; D005026:Ethylene Glycols / Q000494:pharmacology*; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D011744:Pyrimidinones / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
D005026:Ethylene Glycols; D011744:Pyrimidinones; D013844:Thiazoles; D009240:N-Formylmethionine Leucyl-Phenylalanine; C056214:dioctanoyl ethylene glycol; C047505:R 59022; D010770:Phosphotransferases; D019852:Diacylglycerol Kinase; D002118:Calcium