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.