N-protein kinase C isoenzymes may be involved in the regulation of various neutrophil functions.
The role of protein kinase C (PKC) isoenzymes in the regulation of cell functions is largely unknown. We studied the effects of 2-(1H-indol-3-yl)-3- [1-(3-dimethylaminopropyl)-1H-indol-3-yl]-maleinimide (Gö 6850), a selective inhibitor of c- and n-PKC isoenzymes, and 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo[2 ,3- a]pyrrolo[3, 4-c]-carbazole (Gö 6976), an inhibitor of c-PKC isoenzymes, on various human neutrophil functions. Gö 6850 inhibited 4 beta-phorbol 12-myristate 13-acetate (PMA)-, 1,2-dicaprylyl- glycerol- and chemotactic peptide-induced superoxide anion formation with half-maximal effects at 100 nM, 240 nM and 850 nM, respectively. Gö 6850 reverted PMA-mediated inhibition of chemotactic peptide-induced rises in cytosolic Ca2+ concentration with a half-maximal effect at 480 nM. Gö 6850 (1 microM) inhibited PMA-induced lysozyme release by 55%. Gö 6976 had no effect on the parameters studied. Our data suggest the following: (1) n- Rather than c-PKC isoenzymes are involved in the regulation of various human neutrophil functions. (2) Different n-PKC isoenzymes may mediate activation of NADPH oxidase by various stimuli. (3) Different n-PKC isoenzymes may be involved in the mediation of the effects of PMA on various cell functions.
Wenzel-Seifert
K
K
Institut für Pharmakologie, Freie Universität Berlin, Germany.
Schächtele
C
C
Seifert
R
R
D002227:Carbazoles / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D008301:Maleimides / Q000494:pharmacology; D009113:Muramidase / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002227:Carbazoles; D007211:Indoles; D007527:Isoenzymes; D008301:Maleimides; D013481:Superoxides; C081021:Go 6976; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011493:Protein Kinase C; D009113:Muramidase; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate