The effect of new potent selective inhibitors of protein kinase C on the neutrophil respiratory burst.
New potent inhibitors of protein kinase C were found to inhibit protein kinase C isolated from rat brain and human neutrophils, with a large degree of selectivity over cAMP-dependent kinase and Ca2+/calmodulin-dependent kinase. These novel compounds were potent inhibitors of the fluoride, diC8- and formyl-methionyl-leucyl-phenylalanine-mediated respiratory bursts in intact neutrophils. The opsonized zymosan-stimulated burst was only marginally affected by the compounds. These results differ from those obtained in studies with H7 and CI, (which are less potent and less specific protein kinase C inhibitors) and are consistent with the hypothesis that protein kinase C has a role in the transduction mechanism for the neutrophil oxidative burst stimulated with fluoride, formyl-methionyl-leucyl-phenylalanine and diC8.
Twomey
B
B
Department of Pharmacology, University College London, UK.
Muid
R E
RE
Nixon
J S
JS
Sedgwick
A D
AD
Wilkinson
S E
SE
Dale
M M
MM
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000201:enzymology; D002227:Carbazoles / Q000494:pharmacology; D002417:Cattle; D004075:Diglycerides / Q000494:pharmacology; D005459:Fluorides / Q000494:pharmacology; D006801:Humans; D026121:Indole Alkaloids; D007700:Kinetics; D009206:Myocardium / Q000201:enzymology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000097:blood; D051381:Rats; D019311:Staurosporine; D013481:Superoxides / Q000097:blood*; D015054:Zymosan / Q000494:pharmacology
D000470:Alkaloids; D002227:Carbazoles; D004075:Diglycerides; D026121:Indole Alkaloids; C044295:1,2-dioctanoylglycerol; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015054:Zymosan; C049985:staurosporine aglycone; D011493:Protein Kinase C; D019311:Staurosporine; D005459:Fluorides