The protein kinase C inhibitor, K252a, inhibits superoxide production in human neutrophils activated by both PIP2-dependent and -independent mechanisms

Biochem Pharmacol. 1991 May 15;41(10):1449-54. doi: 10.1016/0006-2952(91)90560-r.

Abstract

We report that the putative protein kinase C inhibitor, K252a, at concentrations of 0.2 and 1 microM, inhibited the respiratory burst induced by fluoride and formyl-methionyl-leucyl-phenyl-alanine respectively, both in human neutrophils primed with a subthreshold dose of phorbol myristate acetate and in non-primed neutrophils. In addition, K252a effectively inhibited ConA-zymosan-mediated superoxide generation in Ca2(+)-depleted neutrophils, with virtually maximal inhibition seen at 1 microM. These results suggest that protein kinase C is involved in the putative phosphatidylinositol bisphosphate-independent signal transduction mechanism of the respiratory burst as well as the pathway dependent on phosphatidylinositol bisphosphate hydrolysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism
  • Carbazoles / pharmacology*
  • Concanavalin A / metabolism
  • Humans
  • Indole Alkaloids
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / drug effects*
  • Neutrophils / enzymology
  • Oxygen Consumption / drug effects
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositols / pharmacology*
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Superoxides / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Zymosan / metabolism

Substances

  • Carbazoles
  • Indole Alkaloids
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositols
  • Concanavalin A
  • Superoxides
  • N-Formylmethionine Leucyl-Phenylalanine
  • Zymosan
  • staurosporine aglycone
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate
  • Calcium