Classification of endothelin receptors
| Receptor | ETA |
| Receptor Code | 2.1:ET:1:ETA: |
| Previous names | None |
| Structural information | 7TM |
| h 427 aa, P25101, chr, 4; (Adachi et al., 1991) | |
| r 426 aa, P26684; (Lin et al., 1991) | |
| Functional assays | Vasoconstriction in rat aorta |
| Agonists | Selective: none |
| Agonist potencies | ET-1 = ET-2 > S6b ≫ ET-3 (human coronary artery) |
| Antagonist potencies | BQ123 (pA26.9–7.4; Ihara et al., 1992a) |
| PD155080 (8–8.5;Maguire et al., 1995) | |
| FR139317 (7.3–7.9;Aramori et al., 1993) | |
| PD156707 (8–8.7; = CI1020; Doherty et al., 1995) | |
| SB234551 (9;Ohlstein et al., 1998) | |
| L754142 (7.7–8.7;Williams et al., 1995) | |
| BMS182874 (6.2;Stein et al., 1994) | |
| A127722 (9–10.5; ABT627;Opgenorth et al., 1996) | |
| TBC11251 (8.0; Wu et al., 1997) | |
| LU127043 (7.3; Raschack et al., 1995) | |
| LU135252; (Münter et al., 1996) | |
| Radioligand assays | human, rat and porcine heart; A10 smooth muscle cells |
| Radioligands | 125I-ET-1 (K d = 0.01–5 nM) Davenport, 1997 |
| 125I-PD151242 (0.5 nM) Davenport et al., 1994 | |
| 125I-PD164333 (0.2 nM)Davenport et al., 1998 | |
| 3H-BQ123 (3.2 nM) Ihara et al., 1995 | |
| Transduction mechanisms | G protein-coupled: increase in phosphatidyl inositol turnover with elevation of [Ca2+]i; activation of Ca2+ influx |
| Receptor distribution | Mainly vascular smooth muscle and therefore in all tissues receiving a blood supply, including heart, lung, and brain |
| Tissue functions | Vasoconstriction; positive inotrope, cell proliferation (e.g., smooth muscle, mesangial cells) |
| Phenotypes | Craniofacial and cardiovascular malformations in ETA knockout mice (Clouthier et al., 1998) |
| Receptor | ETB |
| Receptor Code | 2.1:ET:2:ETB: |
| Previous names | None |
| Structural information | 7TM |
| h 442 aa, P24530, chr. 13; (Nakamuta et al., 1991) | |
| r 441 aa, P21451; (Sakurai et al., 1990) | |
| m 442 aa, P48302; (Baynash et al., 1994) | |
| Functional assays | Initial depressor response in vivo, NO release, PI generation; vasoconstriction in some vascular beds depending on species (e.g., rabbit pulmonary artery) |
| Agonists | selective: |
| [Ala1,3,11,15]ET-1; (Saeki et al., 1991) | |
| BQ3020; (Ihara et al., 1992b) | |
| IRL 1620; (Takai et al., 1992) | |
| S6c; (William et al., 1991) | |
| Agonist potencies | ET-1 = ET-2 = ET-3 = S6b (rat glomeruli) |
| Antagonist potencies | IRL2500 (pA2 7.8;Balwierczak et al., 1995) |
| RES7011 (6.0;Tanaka et al., 1994) | |
| BQ788 (6.9; Ishikawa et al., 1994) | |
| Ro468443 (pA2 8.1;Clozel and Breu, 1996) | |
| A192621 (8.1; von Geldern et al., 1999) | |
| Radioligand assays | Brain, lung, placenta, and kidney |
| Radioligands | 125I-ET-1 (K d = 0.01–5 nM) Davenport, 1997 |
| 125I-BQ3020 (0.1 nM) Ihara et al., 1992b | |
| 125I-[Ala1,3,11,15]ET-1 (0.2 nM) Molenaar et al., 1992 | |
| 125I-IRL 1620 (0.02 nM) Watakabe et al., 1992 | |
| Transduction mechanisms | G protein-coupled: increase in phosphotidyl inositol turnover with elevation of [Ca2+]i; activation of Ca2+influx |
| Receptor distribution | Vascular, endothelial cells; high densities present in the brain, lung, heart, and intestine |
| Tissue functions | Vasodilatation, bronchoconstriction, vasoconstriction, cell proliferation (e.g., astrocytes) |
| Phenotypes | Polymorphism (N104I; Tanaka et al., 1998) and mutations (S390R and C109R, Tanaka et al., 1998; W276C, Puffenburger et al., 1994) in human ETB receptor gene in Hirschsprung's disease. ETB knockout mice have aganglionosic megacolon (Hosoda et al., 1994; resembling Hirschsprung's disease), associated with coat color spotting, and are deficient in sensing inflammatory pain (Griswold et al., 1999) |
chr., chromosome; NO, nitric oxide; h, human; m, mouse; r, rat.