title: A potent inhibitor of protein kinase C inhibits natural killer activity.
abstract: A potent inhibitor of protein kinase C(PKC), 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), dose-dependently inhibited natural killer (NK) activity in large granular lymphocytes (LGL) pretreated at 37 degrees C for 30 min. However, neither N-(2-aminoethyl)-5-isoquinolinesulfonamide dihydrochloride (H-9), which inhibits more effectively cyclic nucleotide-dependent protein kinases than other kinases, nor N-(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride (HA1004), which was used as a control for H-7, reduced NK activity. The inhibitor effect of H-7 was not due to changes in effector cell viability or target cell binding. We also found that H-7 suppresses PKC activity in both the cytosol and membrane fractions of LGL. From these findings, PKC is considered to play an essential role in the lytic mechanism of NK cell-mediated cytolysis.
authors.affiliation: Department of Bacteriology, Fukushima Medical College, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: F
authors.initials: F
authors.lastname: Tanabe
authors.forename: A
authors.initials: A
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Takami
authors.forename: S
authors.initials: S
authors.lastname: Shigeta
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002461:Cell Line, Transformed; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013449:Sulfonamides
chemical_list: D007546:Isoquinolines; D010879:Piperazines; D013449:Sulfonamides; C044388:N-(2-aminoethyl)-5-isoquinolinesulfonamide; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D011493:Protein Kinase C