Inhibition of neutrophil superoxide formation by 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), and inhibitor of protein kinase-C.
Superoxide formation of human neutrophils stimulated by phorbol 12-myristate 13-acetate (PMA), N-formyl-methionyl-leucyl-phenylalanine, or calcium ionophore A23187 was inhibited by pretreatment of the cells with 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), an inhibitor of protein kinase-C, but was not inhibited by N-(2-guanidinoethyl)-5-isoquinolinesulfonamide which has a less inhibitory effect on the protein kinase-C. H-7 also inhibited superoxide formation of PMA-activated cytoplasts, which lack nuclei and granules. The phosphorylation of proteins induced by PMA in the cytoplasts as well as the intact neutrophils was also inhibited by preincubation with H-7. Among several phosphoproteins affected by H-7, one protein with a molecular weight of 19,000 (pI = 4.9) was inhibited markedly. N-(2-Guanidinoethyl)-5-isoquinolinesulfonamide did not inhibit the phosphorylation of proteins induced by PMA. These findings support the possibility that the protein kinase-C is involved in the activation process of superoxide formation.
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000001:Calcimycin / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010750:Phosphoproteins / Q000097:blood; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013481:Superoxides / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007546:Isoquinolines; D010750:Phosphoproteins; D010879:Piperazines; D013481:Superoxides; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate