Endothelin B receptors on human endothelial and smooth-muscle cells show equivalent binding pharmacology

J Cardiovasc Pharmacol. 1998 Jul;32(1):106-16. doi: 10.1097/00005344-199807000-00017.


We have described the pharmacologic profiles of endothelin B receptors in human endothelial cells and vascular and nonvascular smooth-muscle cells. First, by amplifying endothelin B receptor numbers through the use of phosphoramidon and intact cell-binding techniques, we demonstrated the presence of these receptors in human umbilical vein endothelial cells (100% endothelin B receptors), human aortic smooth-muscle cells (22% endothelin B, 78% endothelin A receptors), and human bronchial smooth-muscle cells (55% endothelin B, 45% endothelin A receptors) by using [125I]-endothelin-1 radioligand binding. The typical binding profiles of the endothelin B receptors were established through competition binding curve analysis with endothelin-1, endothelin-3, sarafotoxin 6c, and the endothelin A receptor-selective antagonist BQ-123. In the presence of BQ-123, a diverse group of antagonists, including PD 142893, BQ-788, SB 209670, and Ro 47-0203, were used to probe for binding differences indicative of multiple endothelin B-receptor subtypes. The results indicate a rank order of potency for the antagonists of BQ-788 > SB 209670 > PD 142893 > Ro 47-0203 for each cell line, and that between any of these human cell lines, measurements of [125I]-endothelin-1-binding antagonism for each of the four test compounds differed by less than twofold. Although this study cannot discount the possibility of more than one endothelin B-receptor subtype in humans, it does indicate that these tissues express receptors that show equivalent binding pharmacology.

MeSH terms

  • Binding, Competitive / drug effects
  • Bosentan
  • Cells, Cultured
  • Endothelin Receptor Antagonists
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Humans
  • Immunohistochemistry
  • Indicators and Reagents
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism*
  • Oligopeptides / pharmacology
  • Peptides, Cyclic / pharmacology
  • Radioligand Assay
  • Receptor, Endothelin B
  • Receptors, Endothelin / metabolism*
  • Sulfonamides / pharmacology


  • Endothelin Receptor Antagonists
  • Indicators and Reagents
  • Oligopeptides
  • Peptides, Cyclic
  • Receptor, Endothelin B
  • Receptors, Endothelin
  • Sulfonamides
  • PD 142893
  • Bosentan
  • cyclo(Trp-Asp-Pro-Val-Leu)