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Values are the number of amino acids in the predicted receptor protein. Percentages indicate the degree of sequence similarity between receptor types. References: Arai et al., 1990;Sakuri et al., 1990; Hosoda et al., 1991;Kozuka et al., 1991; Lin et al., 1991;Nakamuta et al., 1991; Elshourbagy et al., 1992; Hosoda et al., 1994; Nishimura et al., 1995; Yang et al., 1998.
ETA M-------------------------------------------------ETLCLRASF ETB MQPPPSLCGRALVALVLACGLSRIWGEERGFPPDRA----TP- LLQTAEIMTPPTKTL ETA WLALVGCVISDNPERYSTNLSNHVDDFTTFRGTELSFLVTTHQPTNLVLPSNGSMHNYC ETB W-----------PKGSNASLARSLAPAEVPKGDR----TAGSPPRTISPPP-------C I ETA PQQTKITSAFKYINTVISCTIFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLI ETB QGPIEIKETFKYINTVVSCLVFVLGIIGNSTLLRIIYKNKCMRNGPNILIASLALGDLL II III ETA YVVIDLPINVFKLLAGRWPFDHNDFGVFLCKLFPFLQKSSVGITVLNLCALSVDRYRAV ETB HIVIDIPINVYKLLAEDWPFGAE-----MCKLVPFIQKASVGITVLSLCALSIDRYRAV IV ETA ASWSRVQGIGIPLVTAIEIVSIWILSFILAIPEAIGFVMVPFEYRGEQHKTCMLNATSK ETB ASWSRIKGIGVPKWTAVEIVLIWVVSVVLAVPEAIGFDIITMDYKGSYLRICLLHPVQK ETA --FMEFYQDVKDWWLFGFYFCMPLVCTAIFYTLMTCEMLNRRNGSLRIALSEHLKQRRE ETB TAFMQFYKTAKDWWLFSFYFCLPLAITAFFYTLMTCEML-RKKSGMQIALNDHLKQRRE VI VII ETA VAKTVFCLVVIFALCWFPLHLSRILKKTVYNEMDKNRCELLSFLLLMDYIGINLATMNS ETB VAKTVFCLVLVFALCWLPLHLSRILKLTLYNQNDPNRCELLSFLLVLDYIGINMASLNS ETA CINPIALYFVSKKFKNCFQSCLCCCCYQSKSLMTSVPMNGTSIQWKNHDQNNHNTDRSS ETB CINPIALYLVSKRFKNCFKSCLCCWCQSFEEKQSLEEKQSCLKFKANDHGYDNFRSSNK ETA HKDSMN ETB YSSS Membrane-spanning domains (I–VII) are shown underlined.
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.
In this issue
International Union of Pharmacology. XXIX. Update on Endothelin Receptor Nomenclature
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- Article
- Abstract
- I. Introduction
- II. Cloned Endothelin Receptors
- III. Mammalian Splice Variants of EndothelinA and EndothelinB Receptors
- IV. Physiological Role of Receptors
- V. Endogenous and Synthetic Agonists
- VI. Radiolabeled Agonists
- VII. Antagonists
- VIII. Radiolabeled EndothelinA Selective Antagonists
- IX. EndothelinB Selective Antagonists
- X. EndothelinA/EndothelinB Antagonists
- XI. Conclusions
- Acknowledgments
- Footnotes
- Abbreviations
- References
- Figures & Data
- Info & Metrics
- eLetters