Erbstatin blocks platelet activating factor-induced protein-tyrosine phosphorylation, polyphosphoinositide hydrolysis, protein kinase C activation, serotonin secretion and aggregation of rabbit platelets

FEBS Lett. 1990 Apr 9;263(1):104-8. doi: 10.1016/0014-5793(90)80715-u.

Abstract

The role of protein-tyrosine phosphorylation in the signal transduction of platelet activating factor (PAF) was investigated in rabbit platelets with a range of synthetic compounds that inhibit protein-tyrosine kinases. In particular, erbstatin (IC50 approximately 20 micrograms/ml) abrogated a wide range of platelet responses to PAF, including tyrosine phosphorylation of cellular proteins, polyphosphoinositide turnover, activation of membranous protein kinase C, platelet aggregation, and serotonin secretion. With about a third of the potency of erbstatin, compound RG50864 also inhibited many of these responses, whereas at 100 micrograms/ml, genistein, 670C88 and ST271 were without effect. Finally, the ability of thrombin to cause platelet aggregation and serotonin secretion was also compromised by erbstatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies
  • Blood Platelets / drug effects
  • Blood Platelets / physiology*
  • Enzyme Activation
  • Hydrolysis
  • Hydroquinones / pharmacology*
  • In Vitro Techniques
  • Kinetics
  • Phosphatidylinositol Phosphates
  • Phosphatidylinositols / blood*
  • Phosphorylation
  • Phosphotyrosine
  • Platelet Activating Factor / pharmacology*
  • Platelet Aggregation
  • Platelet Aggregation Inhibitors / pharmacology*
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / blood*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / blood*
  • Rabbits
  • Serotonin / blood*
  • Tyrosine / analogs & derivatives
  • Tyrosine / analysis

Substances

  • Antibodies
  • Hydroquinones
  • Phosphatidylinositol Phosphates
  • Phosphatidylinositols
  • Platelet Activating Factor
  • Platelet Aggregation Inhibitors
  • Phosphotyrosine
  • Serotonin
  • Tyrosine
  • Protein-Tyrosine Kinases
  • Protein Kinase C
  • erbstatin