The protein kinase C inhibitor, K252a, inhibits superoxide production in human neutrophils activated by both PIP2-dependent and -independent mechanisms.
We report that the putative protein kinase C inhibitor, K252a, at concentrations of 0.2 and 1 microM, inhibited the respiratory burst induced by fluoride and formyl-methionyl-leucyl-phenyl-alanine respectively, both in human neutrophils primed with a subthreshold dose of phorbol myristate acetate and in non-primed neutrophils. In addition, K252a effectively inhibited ConA-zymosan-mediated superoxide generation in Ca2(+)-depleted neutrophils, with virtually maximal inhibition seen at 1 microM. These results suggest that protein kinase C is involved in the putative phosphatidylinositol bisphosphate-independent signal transduction mechanism of the respiratory burst as well as the pathway dependent on phosphatidylinositol bisphosphate hydrolysis.
Twomey
B M
BM
Department of Pharmacology, University College London, U.K.
Clay
K
K
Dale
M M
MM
D002118:Calcium / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology*; D003208:Concanavalin A / Q000378:metabolism; D006801:Humans; D026121:Indole Alkaloids; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D010101:Oxygen Consumption / Q000187:drug effects; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan / Q000378:metabolism
D002227:Carbazoles; D026121:Indole Alkaloids; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D003208:Concanavalin A; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan; C049985:staurosporine aglycone; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium