title: Effects of a protein kinase C inhibitor, K-252a, on human polymorphonuclear neutrophil responsiveness.
abstract: We investigated the capacity of K-252a, an inhibitor of rat brain protein kinase C (PKC), to influence polymorphonuclear neutrophil (PMN) PKC and PMN activation with chemically and structurally dissimilar agonists. K-252a inhibited PMN PKC (IC50 = 0.58 microM), and caused a concentration-dependent (0.1-10 microM) inhibition of degranulation elicited with the chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP), the lipid agonists, 5(S), 12(R)-dihydroxy-5,14-cis-8,10-trans eicosatetraenoic acid (LTB4) and acetyl-sn-glyceryl-3-phosphorylcholine (AGEPC), and phorbol 12-myristate 13-acetate. Superoxide anion (O2-) production by PMNs exposed to these stimuli as well as sn-1,2-dioctanoylglycerol (diC8) was also suppressed by K-252a. PMN PKC activity was inhibited with concentrations of K-252a which suppressed PMN responsiveness. Therefore, K-252a appears to be a useful probe for examining the role of PKC in the underlying pathway(s) of PMN activation.
authors.affiliation: Department of Hypersensitivity Diseases Research, Upjohn Company, Kalamazoo, MI 49001.
authors.forename: R J
authors.initials: RJ
authors.lastname: Smith
authors.forename: J M
authors.initials: JM
authors.lastname: Justen
authors.forename: L M
authors.initials: LM
authors.lastname: Sam
mesh_terms: D002227:Carbazoles / Q000494:pharmacology*; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D005089:Exocytosis; D006801:Humans; D026121:Indole Alkaloids; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013481:Superoxides / Q000097:blood
chemical_list: D002227:Carbazoles; D026121:Indole Alkaloids; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; C049985:staurosporine aglycone; D011493:Protein Kinase C