A novel conformationally restricted protein kinase C inhibitor, Ro 31-8425, inhibits human neutrophil superoxide generation by soluble, particulate and post-receptor stimuli

FEBS Lett. 1991 Nov 18;293(1-2):169-72. doi: 10.1016/0014-5793(91)81178-b.


A novel, bis-indolylmaleimide, Ro 31-8425, bearing a conformationally restricted side chain, inhibits protein kinase C isolated from rat brain and human neutrophils with a high degree of selectivity over cAMP-dependent kinase and Ca2+/calmodulin-dependent kinase. It also inhibits phorbol ester-induced intracellular events known to be mediated by protein kinase C (p47 phosphorylation in intact platelets, CD3 and CD4 down-regulation in T-cells). Ro 31-8425 inhibited superoxide generation in human neutrophils activated by both receptor stimuli (formyl-methionyl-leucylphenylalanine, opsonized zymosan, IgG and heat aggregated IgG) and post-receptor stimuli (1,2-dioctanoylglycerol and fluoride). The compound also blocked antigen driven, but not IL-2 induced, T-cell proliferation. These results support a central role for protein kinase C in the activation of the respiratory burst and antigen-driven T-cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / enzymology
  • Cattle
  • Humans
  • Indoles / pharmacology*
  • Maleimides / pharmacology*
  • Neutrophils / drug effects*
  • Neutrophils / enzymology
  • Neutrophils / metabolism
  • Protein Conformation
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / chemistry*
  • Rabbits
  • Rats
  • Receptors, Cell Surface / drug effects*
  • Receptors, Cell Surface / metabolism
  • Respiratory Burst / drug effects
  • Solubility
  • Superoxides / antagonists & inhibitors*
  • Superoxides / blood


  • Indoles
  • Maleimides
  • Receptors, Cell Surface
  • Superoxides
  • Ro 31-8425
  • Protein Kinase C
  • Ro 31-7549