E5510 antagonizes thrombin receptor signals by inhibiting NF-kappa B activation

Biochem Biophys Res Commun. 1994 Sep 15;203(2):1181-7. doi: 10.1006/bbrc.1994.2307.

Abstract

We have recently demonstrated that NF-kappa B is involved in a thrombin-signaling and that the antisense oligodeoxynucleotides (ODNs) of NF-kappa B has a marked inhibitory effect on thrombin-induced cellular responses. In this study, we demonstrate that E5510 (4-cyano-5,5-bis(methoxyphenyl)-4-pentenoic acid), a compound with anti-platelet activity preferentially inhibits the thrombin-inducible NF-kappa B activation and then antagonizes the following thrombin-induced cellular responses, proliferation and cytokines production in vascular smooth muscle cell, and the adherency of differentiated HL-60 cells. These data suggest that E5510 is an anti-atherosclerotic or anti-restenotic drug induced by thrombin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins*
  • Cell Adhesion / drug effects
  • Cell Differentiation
  • Cell Division / drug effects
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Fatty Acids, Monounsaturated / pharmacology*
  • Humans
  • Molecular Sequence Data
  • Muscle, Smooth, Vascular / metabolism
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / physiology
  • Platelet Aggregation Inhibitors / pharmacology*
  • RNA-Binding Proteins / pharmacology
  • Receptors, Thrombin / antagonists & inhibitors*
  • Thrombin / antagonists & inhibitors
  • Thrombin / pharmacology
  • Transcription Factors / pharmacology
  • Tumor Cells, Cultured

Substances

  • Bacterial Proteins
  • Cytokines
  • Fatty Acids, Monounsaturated
  • MtrB protein, Bacteria
  • NF-kappa B
  • Platelet Aggregation Inhibitors
  • RNA-Binding Proteins
  • Receptors, Thrombin
  • Transcription Factors
  • Thrombin
  • Satigrel