The bradykinin B2 receptor antagonist WIN 64338 inhibits the effect of des-Arg9-bradykinin in endothelial cells

Eur J Pharmacol. 1994 Dec 15;288(1):R1-2. doi: 10.1016/0922-4106(94)90017-5.

Abstract

WIN 64338 (phosphonium, [[4-[[2-[[bis(cyclohexylamino) methylene] amino]-3-(2-naphthalenyl) 1-oxopropyl]amino]-phenyl]- tributyl, chloride, monohydrochloride) is the first potent nonpeptide competitive bradykinin B2 receptor antagonist as shown in classical pharmacological preparations with no activity in the rabbit aorta stimulated by the bradykinin B1 receptor agonist des-Arg9-bradykinin. In primary cultured bovine aortic endothelial cells, both bradykinin and des-Arg9-bradykinin stimulate the production of intracellular cyclic GMP, an index for the production of nitric oxide. Surprisingly, WIN 64338 did not inhibit bradykinin but abolished the effect of des-Arg9-bradykinin suggesting that kinin receptor antagonists do not necessarily discriminate between kinin receptor subtypes in an identical way in different tissues and species.

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Binding, Competitive
  • Bradykinin / analogs & derivatives*
  • Bradykinin / metabolism
  • Bradykinin / pharmacology
  • Bradykinin Receptor Antagonists*
  • Cattle
  • Cells, Cultured
  • Cyclic GMP / biosynthesis
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Naphthalenes / metabolism
  • Naphthalenes / pharmacology*
  • Nitric Oxide / biosynthesis
  • Organophosphorus Compounds / metabolism
  • Organophosphorus Compounds / pharmacology*
  • Rabbits

Substances

  • Bradykinin Receptor Antagonists
  • Naphthalenes
  • Organophosphorus Compounds
  • WIN 64338
  • bradykinin, des-Arg(9)-
  • Nitric Oxide
  • Cyclic GMP
  • Bradykinin