Endothelin Receptors

The endothelin family consists of highly potent vasoconstrictive peptides. Three endogenous isoforms are known to exist - ET-1, ET-2 and ET-3. Due to their physiological role as vasoactive peptides, endothelins have been linked to certain cardiac, vascular and renal diseases; endothelin antagonists may therefore play an important role in the treatment of these conditions. Two distinct endothelin receptors have so far been cloned in mammals, classified as ETA and ETB receptors.

Targets
Literature
Receptor Data

Endothelin Receptor Target Files

Endothelin receptors are widely expressed in all tissues. They are also localized to non-vascular structures including epithelial cells, glia and neurons. The principal physiological role of endothelin receptors is the maintenance of vascular tone. They also have comitogenic activity, potentiating the effects of other growth factors such as PDGF.

Literature for Endothelin Receptors

Cardiovascular

Cardiovascular Research Product Guide

A collection of over 250 products for cardiovascular research, the guide includes research tools for the study of:

  • Hypertension
  • Thrombosis and Hemostasis
  • Atherosclerosis
  • Myocardial Infarction
  • Ischemia/Reperfusion Injury
  • Arrhythmias
  • Heart Failure
GPCR

GPCR Product Listing

A collection of over 450 products for G protein-coupled receptors, the listing includes research tools for the study of:

  • Rhodopsin-like Receptors
  • Secretin-like Receptors
  • Glutamate Receptors
  • Frizzled Receptors
  • GPCR Signaling
Peptide Hormone Receptors

Peptide Hormone Receptors Product Listing

A collection of over 200 products for peptide hormone receptors, the listing includes research tools for the study of:

  • Anterior Pituitary Regulation
  • Blood Pressure Regulation
  • Feeding and Appetite Regulation
  • Glucose Regulation
  • Peptide Hormone Processing

Endothelin Receptor Data

Receptor Subtype ETA Receptors ETB Receptors
Transduction Mechanism 7-TM, ↑ PI turnover → ↑ Ca2+i.c., ↑ Ca2+ influx 7-TM, ↑ PI turnover → ↑ Ca2+i.c., ↑ Ca2+ influx
Primary Locations Vascular smooth muscle Vascular endothelial cells
Tissue Functions Vasoconstriction, positive ionotrope, cell proliferation Vasodilatation, bronchoconstriction, vasoconstriction, cell proliferation
Endogenous Ligand Potency ET-1 = ET-2 > ET-3 ET-1 = ET-2 = ET-3

Key Compounds Ki Values (nM)
Selective ETB Agonists IRL-1620 (1196)
Sarafotoxin S6c (1175)
BQ-3020 (1189)
[Ala1,3,11,15]-Endothelin (1197)
1190
2800
970
2200*
0.016
0.29
0.18
0.33*
ETA Antagonists BQ-123 (1188)
FR 139317 (1210)
BMS 182874 (1441)
Sulfisoxazole (0731)
CI 1020 (2942)
1.4
1
48
600*
0.3*
1500
7300
> 50000
2200*
480*

* IC50 values

References

Davenport (2000) International Union of Pharmacology. XXIX. Update on endothelin receptor nomenclature. Pharmacol.Rev. 54 219. Takai et al (1992) A potent and specific agonist, Suc-[Glu9,Ala11,15]-endothelin-1(8-21), IRL 1620, for the ETB receptor. Biochem.Biophys.Res.Comm. 184 953. Williams et al (1993) Characterization of cloned human endothelin receptors. Life Sci. 53 407. Ihara et al (1995) [3H]-BQ-123, a highly specific and reversible radioligand for the endothelin ETA receptor subtype. Eur.J.Pharmacol. 274 1. Reynolds et al (1995) Pharmacological differences between rat and human endothelin B receptors. Biochem.Biophys.Res.Comm. 209 506. Nakamichi et al (1992) Different distribution of endothelin receptor subtypes in pulmonary tissues revealed by the novel selective ligands BQ-123 and [Ala1,3,11,15]ET-1. Biochem.Biophys.Res.Comm. 182 144. Makatani et al (2000) Effect of a novel bifunctional endothelin receptor antagonist, IRL 3630A, on guinea pig respiratory mechanics. Eur.J.Pharmacol. 406 139. Aramori et al (1993) Subtype selectivity of a novel endothelin antagonist, FR 139317, for the two endothelin receptors in transfected Chinese hamster ovary cells. Mol.Pharmacol. 43 127. Webb et al (1995) BMS-182874 is a selective, nonpeptide endothelin ETA receptor antagonist. J.Pharmacol.Exp.Ther. 272 1124. Chan et al (1994) Identification of a new class of ETA selective endothelin antagonists by pharmacophore screening. Biochem.Biophys.Res.Comm. 201 228.