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Effects of a protein kinase C inhibitor, K-252a, on human polymorphonuclear neutrophil responsiveness. 1988

R J Smith, and J M Justen, and L M Sam
Department of Hypersensitivity Diseases Research, Upjohn Company, Kalamazoo, MI 49001.

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.

UI MeSH Term Description Entries
D009240 N-Formylmethionine Leucyl-Phenylalanine A formylated tripeptide originally isolated from bacterial filtrates that is positively chemotactic to polymorphonuclear leucocytes, and causes them to release lysosomal enzymes and become metabolically activated. F-Met-Leu-Phe,N-Formyl-Methionyl-Leucyl-Phenylalanine,Formylmet-Leu-Phe,Formylmethionyl Peptide,Formylmethionyl-Leucyl-Phenylalanine,Formylmethionylleucylphenylalanine,N-Formylated Peptide,N-formylmethionyl-leucyl-phenylalanine,fMet-Leu-Phe,F Met Leu Phe,Formylmet Leu Phe,Formylmethionyl Leucyl Phenylalanine,Leucyl-Phenylalanine, N-Formylmethionine,N Formyl Methionyl Leucyl Phenylalanine,N Formylated Peptide,N Formylmethionine Leucyl Phenylalanine,N formylmethionyl leucyl phenylalanine,Peptide, Formylmethionyl,Peptide, N-Formylated,fMet Leu Phe
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D002227 Carbazoles Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.
D003594 Cytoplasmic Granules Condensed areas of cellular material that may be bounded by a membrane. Cytoplasmic Granule,Granule, Cytoplasmic,Granules, Cytoplasmic
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005089 Exocytosis Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013481 Superoxides Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides. Superoxide Radical,Superoxide,Superoxide Anion
D026121 Indole Alkaloids Group of alkaloids containing a benzylpyrrole group (derived from TRYPTOPHAN). Indole Alkaloid,Alkaloid, Indole,Alkaloids, Indole

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