A novel ETA antagonist (BQ-123) inhibits endothelin-1-induced phosphoinositide breakdown and DNA synthesis in rat vascular smooth muscle cells

FEBS Lett. 1992 May 18;302(3):243-6. doi: 10.1016/0014-5793(92)80451-l.

Abstract

The effects of a novel cyclic pentapeptide (BQ-123), an endothelin (ET) antagonist selective for the ETA receptor subtype, on phosphoinositide breakdown and DNA synthesis stimulated by ET-1 were studied in cultured rat vascular smooth muscle cells (VSMC). BQ-123 competitively inhibited the binding of [125I]ET-1 to VSMC with the apparent Ki of 4 x 10(-9) M. BQ-123 dose-dependently inhibited formation of inositol-1,4,5-trisphosphate and [3H]thymidine uptake stimulated by ET-1. These data suggest that the ET-1-induced DNA synthesis in VSMC is mainly mediated by ETA receptor subtype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Cells, Cultured
  • DNA / biosynthesis*
  • Endothelins / antagonists & inhibitors
  • Endothelins / metabolism
  • Endothelins / pharmacology*
  • Male
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism*
  • Peptides, Cyclic / pharmacology*
  • Phosphatidylinositols / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Cell Surface / antagonists & inhibitors*
  • Receptors, Endothelin

Substances

  • Endothelins
  • Peptides, Cyclic
  • Phosphatidylinositols
  • Receptors, Cell Surface
  • Receptors, Endothelin
  • DNA
  • cyclo(Trp-Asp-Pro-Val-Leu)