Table 3

Classification of endothelin receptors

 Receptor Code2.1:ET:1:ETA:
 Previous namesNone
 Structural information7TM
h 427 aa, P25101, chr, 4; (Adachi et al., 1991)
r 426 aa, P26684; (Lin et al., 1991)
 Functional assaysVasoconstriction in rat aorta
 AgonistsSelective: none
 Agonist potenciesET-1 = ET-2 > S6b ≫ ET-3 (human coronary artery)
 Antagonist potenciesBQ123 (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 assayshuman, 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 mechanismsG protein-coupled: increase in phosphatidyl inositol turnover with elevation of [Ca2+]i; activation of Ca2+ influx
 Receptor distributionMainly vascular smooth muscle and therefore in all tissues receiving a blood supply, including heart, lung, and brain
 Tissue functionsVasoconstriction; positive inotrope, cell proliferation (e.g., smooth muscle, mesangial cells)
 PhenotypesCraniofacial and cardiovascular malformations in ETA knockout mice (Clouthier et al., 1998)
 Receptor Code2.1:ET:2:ETB:
 Previous namesNone
 Structural information7TM
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 assaysInitial depressor response in vivo, NO release, PI generation; vasoconstriction in some vascular beds depending on species (e.g., rabbit pulmonary artery)
[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 potenciesET-1 = ET-2 = ET-3 = S6b (rat glomeruli)
 Antagonist potenciesIRL2500 (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 assaysBrain, 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 mechanismsG protein-coupled: increase in phosphotidyl inositol turnover with elevation of [Ca2+]i; activation of Ca2+influx
 Receptor distributionVascular, endothelial cells; high densities present in the brain, lung, heart, and intestine
 Tissue functionsVasodilatation, bronchoconstriction, vasoconstriction, cell proliferation (e.g., astrocytes)
 PhenotypesPolymorphism (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.