An endothelin B receptor-selective antagonist: IRL 1038, [Cys11-Cys15]-endothelin-1(11-21)

FEBS Lett. 1992 Oct 12;311(1):12-6. doi: 10.1016/0014-5793(92)81355-p.

Abstract

In the inhibition of specific binding of [125I]endothelins (ETs) to membrane from various tissues of rats, guinea pigs, pigs and humans, [Cys11-Cys15]-ET-1(11-21), IRL 1038, has a much higher affinity for ETB receptors (Ki = 6-11 nM) than for ETA receptors (Ki = 0.4-0.7 microM). In contraction assays, with ET-3 as a stimulant, 3 microM IRL 1038 antagonized the ETB receptor-mediated contraction of guinea pig ileal and tracheal smooth muscle without any significant agonistic activity, but did not effect the ETA receptor-mediated contraction of rat aortic smooth muscle. IRL 1038 is therefore, considered to be the first antagonist selective to the ETB receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biological Assay
  • Cystine
  • Disulfides
  • Dose-Response Relationship, Drug
  • Endothelin Receptor Antagonists*
  • Endothelins / chemical synthesis
  • Endothelins / metabolism*
  • Endothelins / pharmacology*
  • Guinea Pigs
  • Humans
  • Ligands
  • Membranes / metabolism
  • Molecular Sequence Data
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Organ Specificity
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / pharmacology*
  • Rats
  • Receptors, Endothelin / metabolism*
  • Sensitivity and Specificity
  • Sequence Homology, Amino Acid
  • Swine

Substances

  • Disulfides
  • Endothelin Receptor Antagonists
  • Endothelins
  • Ligands
  • Peptide Fragments
  • Receptors, Endothelin
  • Cys(11)-Cys(15)-endothelin-1 (11-21)
  • Cystine