Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Endothelin A Receptor (ETAR)

  • Randa Hilal-DandanEmail author
  • Laurence L. Brunton
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_616


Historical Background

Endothelin-1 (ET-1) is a 21-amino-acid vasoactive peptide (see structure in Table 1) that was first isolated and identified in 1988 from porcine aortic endothelial cells. The endothelin family consists of three isoforms: ET-1, ET-2, and ET-3. ET-1 is the principal isoform and is a very potent vasoconstrictor and growth promoter. The physiological effects of the ET system are many and include regulation of vascular tone, renal function, and cell proliferation. ET exerts its effects through two types of endothelin receptors: type A (ETAR) and type B (ETBR). ETAR and ETBR are G-protein-coupled receptors (GPCRs) that share homology with the rhodopsin family. ETAR is pharmacologically distinguished...
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  1. Abman SH. Role of endothelin receptor antagonists in the treatment of pulmonary arterial hypertension. Annu Rev Med. 2009;60:13–23.CrossRefPubMedGoogle Scholar
  2. Bagnato A, Loizidou M, Pflug BR, Curwen J, Growcott J. Role of the endothelin axis and its antagonists in the treatment of cancer. Br J Pharmacol. 2011;163:220–33.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Barnes PJ. Pulmonary pharmacology. In: Brunton L, Chabner B, Knollmann B, editors. The pharmacological basis of therapeutics. 12th ed. New York: McGraw-Hill; 2011. p. 1031–66.Google Scholar
  4. Barton M, Yanagisawa M. Endothelin: 20 years from discovery to therapy. Can J Physiol Pharmacol. 2008;86:485–98.CrossRefPubMedGoogle Scholar
  5. Bkaily G, Avedanian L, Al-Khoury J, Provost C, Nader M, D'Orléans-Juste P, Jacques D. Nuclear membrane receptors for ET-1 in cardiovascular function. Am J Phys. 2011;300:R251–63.Google Scholar
  6. Davenport AP. International Union of Pharmacology. XXIX. Update on endothelin receptor nomenclature. Pharmacol Rev. 2002;54:219–26.CrossRefPubMedGoogle Scholar
  7. Dhaun N, Macintyre IM, Kerr D, Melville V, Johnston NR, Haughie S, et al. Selective endothelin-a receptor antagonism reduces proteinuria, blood pressure, and arterial stiffness in chronic proteinuric kidney disease. Hypertension. 2011;57:772–9.CrossRefPubMedGoogle Scholar
  8. Edvinsson L, Povlsen GK. Late cerebral ischaemia after subarachnoid haemorrhage: is cerebrovascular receptor upregulation the mechanism behind? Acta Physiol (Oxford). 2011;203:209–24.CrossRefGoogle Scholar
  9. Evans NJ, Walker JW. Endothelin receptor dimers evaluated by FRET, ligand binding, and calcium mobilization. Biophys J. 2008;95:483–92.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Hilal-Dandan R, Brunton LL. Endothelin type A receptor. 2010. http://www.signaling-gateway.org/molecule/query?afcsid=A.000836. Accessed 30 Mar 2011.
  11. Hilal-Dandan R, Ramirez MT, Villegas S, Gonzalez A, Endo-Mochizuki Y, Brown JH, et al. Endothelin ETA receptor regulates signaling and ANF gene expression via multiple G protein-linked pathways. Am J Phys. 1997;272:H130–7.Google Scholar
  12. Ivey ME, Osman N, Little PJ. Endothelin-1 signalling in vascular smooth muscle: pathways controlling cellular functions associated with atherosclerosis. Atherosclerosis. 2008;199:237–47.CrossRefPubMedGoogle Scholar
  13. Khimji AK, Rockey DC. Endothelin – biology and disease. Cell Signal. 2010;22:1615–25.CrossRefPubMedGoogle Scholar
  14. Khodorova A, Montmayeur JP, Strichartz G. Endothelin receptors and pain. J Pain. 2009;10:4–28.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Kohan DE. Endothelin, hypertension and chronic kidney disease: new insights. Curr Opin Nephrol Hypertens. 2010;19:134–9.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Kuc RE, Maguire JJ, Davenport AP. Quantification of endothelin receptor subtypes in peripheral tissues reveals downregulation of ET(A) receptors in ET(B)-deficient mice. Exp Biol Med (Maywood). 2006;231:741–5.Google Scholar
  17. Motte S, McEntee K, Naeije R. Endothelin receptor antagonists. Pharmacol Ther. 2006;110:386–414.CrossRefPubMedGoogle Scholar
  18. Paasche JD, Attramadal T, Kristiansen K, Oksvold MP, Johansen HK, Huitfeldt HS, et al. Subtype-specific sorting of the ETA endothelin receptor by a novel endocytic recycling signal for G protein-coupled receptors. Mol Pharmacol. 2005;67:1581–90.CrossRefPubMedGoogle Scholar
  19. Rosano L, Cianfrocca R, Masi S, Spinella F, Di Castro V, Biroccio A, et al. Beta-arrestin links endothelin A receptor to beta-catenin signaling to induce ovarian cancer cell invasion and metastasis. Proc Natl Acad Sci U S A. 2009;106:2806–11.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Sato T, Kurihara Y, Asai R, Kawamura Y, Tonami K, Uchijima Y, et al. An endothelin-1 switch specifies maxillomandibular identity. Proc Natl Acad Sci U S A. 2008;105:18806–11.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Schneider MP, Boesen EI, Pollock DM. Contrasting actions of endothelin ET(A) and ET(B) receptors in cardiovascular disease. Annu Rev Pharmacol Toxicol. 2007;47:731–59.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Takigawa M, Sakurai T, Kasuya Y, Abe Y, Masaki T, Goto K. Molecular identification of guanine-nucleotide-binding regulatory proteins which couple to endothelin receptors. Eur J Biochem. 1995;228:102–8.CrossRefPubMedGoogle Scholar

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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.PharmacologyUniversity of California San DiegoSan DiegoUSA