Endothelin receptors in the human coronary artery, ventricle and atrium. A quantitative autoradiographic analysis

Naunyn Schmiedebergs Arch Pharmacol. 1993 Oct;348(4):403-10. doi: 10.1007/BF00171340.

Abstract

In the present experiments we investigated endothelin (ET) receptors in the human coronary artery, and in ventricular and atrial muscle using quantitative receptor autoradiography. Displacement of [125I]Sf6b (Sarafotoxin S6b) (30 pM)- and [125I]ET-1 (30 pM)-labeled binding sites was studied using ET-1, the ETA receptor selective ligand BQ-123 (cyclo[D-Asp-L-Pro-D-Val-L-Leu-D-Trp-]), and the ETB receptor selective ligand [Ala1, 3, 11, 15]ET-1. Specific binding was more dense in atrium and coronary artery (relative optical density (r.o.d.): 0.14 +/- 0.01 and 0.16 +/- 0.01, respectively) than in ventricular muscle (r.o.d.: 0.10 +/- 0.01). In the coronary artery, binding was especially dense in the media. ET-1 displaced [125I]ET-1 and [125I]Sf6b monophasically in atrium, ventricle and coronary artery. [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I]ET-1 and [125I]Sf6b-labeled sites biphasically in the ventricle and in the atrium. In the human coronary artery, [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I]ET-1-labeled sites monophasically (pIC50: ET-1 (9.72 +/- 0.12) > BQ-123 (6.84 +/- 0.08) > [Ala1,3,11,15]ET-1 (6.40 +/- 0.12). In contrast, [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I]Sf6b-labeled coronary artery sites biphasically (high affinity pIC50: BQ-123, 9.03 +/- 0.25; [Ala1,3,11,15]ET-1, 8.40 +/- 0.14; low affinity pIC50: BQ-123, 7.24 +/- 0.14; [Ala1,3,11,15]ET-1, 6.99 +/- 0.09). These data indicate that both [125I]ET-1 and [125I] Sf6b-labeled ETA and ETB binding sites in human ventricular and atrial muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Autoradiography
  • Binding, Competitive / drug effects
  • Child
  • Coronary Vessels / anatomy & histology
  • Coronary Vessels / metabolism*
  • Endothelin Receptor Antagonists
  • Female
  • Heart / anatomy & histology
  • Heart Atria / anatomy & histology
  • Heart Atria / metabolism
  • Heart Ventricles / anatomy & histology
  • Heart Ventricles / metabolism
  • Humans
  • In Vitro Techniques
  • Iodine Radioisotopes
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Myocardium / metabolism*
  • Peptides, Cyclic / pharmacology
  • Receptors, Endothelin / metabolism*
  • Vasoconstrictor Agents / pharmacology
  • Viper Venoms / pharmacology

Substances

  • Endothelin Receptor Antagonists
  • Iodine Radioisotopes
  • Peptides, Cyclic
  • Receptors, Endothelin
  • Vasoconstrictor Agents
  • Viper Venoms
  • sarafotoxins s6
  • cyclo(Trp-Asp-Pro-Val-Leu)