In vitro characterization of Ro 46-2005, a novel synthetic non-peptide endothelin antagonist of ETA and ETB receptors

FEBS Lett. 1993 Nov 15;334(2):210-4. doi: 10.1016/0014-5793(93)81713-a.

Abstract

Ro 46-2005 is a new synthetic non-peptide endothelin (ET) receptor antagonist. In binding experiments, Ro 46-2005 proved to be equipotent (IC50 200-500 nM) for inhibition of [125]ET-1 binding on the two known ET receptor subtypes (ETA and ETB). Scatchard analysis was consistent with a competitive binding mode. Ro 46-2005 also inhibited the functional consequences of ET-1 stimulation: the ET-1 induced release of arachidonic acid from rat mesangial cells was inhibited with an IC50 of 1.8 microM.

MeSH terms

  • Animals
  • Aorta / metabolism
  • Arachidonic Acid / metabolism
  • Binding, Competitive
  • Cell Line
  • Cells, Cultured
  • Cerebellum / metabolism
  • Endothelin Receptor Antagonists*
  • Endothelins / metabolism*
  • Female
  • Glomerular Mesangium / drug effects
  • Glomerular Mesangium / metabolism*
  • Humans
  • Intracellular Membranes / metabolism
  • Kinetics
  • Microsomes / metabolism
  • Moths
  • Muscle, Smooth / metabolism*
  • Muscle, Smooth, Vascular / metabolism*
  • Placenta / metabolism
  • Pregnancy
  • Pyrimidines / pharmacology*
  • Rats
  • Receptors, Endothelin / metabolism*
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / metabolism
  • Sulfonamides / pharmacology*
  • Swine
  • Transfection

Substances

  • Endothelin Receptor Antagonists
  • Endothelins
  • Pyrimidines
  • Receptors, Endothelin
  • Recombinant Proteins
  • Sulfonamides
  • Ro 46-2005
  • Arachidonic Acid