Endothelin Receptors and Receptor Antagonists

  • Andrew S. Tasker
  • David M. Pollock

Abstract

Multiple receptor subtypes for endothelin have been identified in pharmacological studies both in vitro and in vivo. As can be evidenced in the study by Yanagisawa et al, at least two receptor subtypes may be responsible for the biphasic nature of the hemodynamic response to intravenous injection of ET-1: a transient hypotension followed by a sustained increase in arterial pressure.1 ET-1 and ET-2 are more active than ET-3 as pressor agents and as constrictors of many isolated vascular preparations.2 ET-1 and ET-3 have similar potencies in terms of transient hypotensive effects that are thought to be mediated by the release of nitric oxide and/or prostaglandins.3,4 These results led to the initial sub-classification of ET receptors as ETA (ET-1-selective located on vascular smooth muscle) and ETB (nonisopeptide-selective located on endothelial cells) which are generally responsible for vasoconstriction and vasodilation, respectively.

Keywords

Fermentation Prostaglandin Streptomyces Hunt Naphthalene 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Yanagisawa M, Kurihara H, Kimura S et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature (London) 1988; 332; 411–415.CrossRefGoogle Scholar
  2. 2.
    Inoue A, Yanagisawa M, Takuwa Y et al. The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci USA 1989; 86: 2863–2867.PubMedCrossRefGoogle Scholar
  3. 3.
    Warner TD, Mitchell JA, de Nucci G et al. Endothelin-1 and endothelin-3 release EDRF from isolated perfused arterial vessels of the rat and rabbit. J Cardiovasc Pharmacol 1989; 13: S85 - S88.PubMedCrossRefGoogle Scholar
  4. 4.
    Gardiner SM, Compton AM, Bennett T. Effects of indomethacin on the regional haemodynamic responses to low doses of endothelins and sarafotoxin. Br J Pharmacol 1990; 100: 158–162.PubMedCrossRefGoogle Scholar
  5. 5.
    Arai H, Nori S, Aramori I et al. Cloning and expression of a cDNA encoding an endothelin receptor. Nature (London) 1990; 348: 730–732.CrossRefGoogle Scholar
  6. 6.
    Sakurai T, Yanagisawa M, Takuwa Y et al. Cloning of a cDNA encoding a nonisopeptide-selective subtype of the endothelin receptor. Nature (London) 1990; 348: 732–735.CrossRefGoogle Scholar
  7. 7.
    Masaki T, Vane JR, Vanhoutte PM. V. International Union of Pharmacology Nomenclature of Endothelin Receptors. Pharmacol Rev 1994; 46: 137–142.PubMedGoogle Scholar
  8. 8.
    Pollock DM, Opgenorth TJ. Evidence for endothelin-induced renal vasoconstriction independent of ETA receptor activation. Am J Physiol 1993; 264, R222 - R226.PubMedGoogle Scholar
  9. 9.
    Bigaud M, Pelton JT. Discrimination between ETA- and ETB-receptor-mediated effects of endothelin-i and [A1a1,3,11,~5)endothelin-1 by BQ-123 in the anesthetized rat. Br J Pharmacol 1992; 107: 912–918.PubMedCrossRefGoogle Scholar
  10. 10.
    Clozel M, Gray GA, Breu V et al. The endothelin ETB receptor mediates both vasodilation and vasoconstriction in vivo. Biochem Biophys Res Comm 1992; 186: 867–873.PubMedCrossRefGoogle Scholar
  11. 11.
    Cristol J-P, Warner TD, Thiemermann C et al. Mediation via different receptors of the vasoconstrictor effects of endothelins and sarafotoxins in the systemic circulation and renal vasculature of the anaesthetized rat. Br J Pharmacol 1993; 108: 776–779.PubMedCrossRefGoogle Scholar
  12. 12.
    Warner TD, Allcock GH, Corder R et al. Use of the endothelin antagonists BQ123 and PD 142893 to reveal three endothelin receptors mediating smooth muscle contraction and the release of EDRF. Br J Pharmacol 1993; 110: 777–782.PubMedCrossRefGoogle Scholar
  13. 13.
    Gray GA, Clozel M. Three endothelin receptor subtypes suggested by the differential potency of bosentan, a novel endothelin receptor antagonist, in isolated tissues. Br J Pharmacol 1994; 112: U62.Google Scholar
  14. 14.
    Sokolovsky M, Ambar I, Galron R. A novel subtype of endothelin receptors. J Biol Chem 1992; 267: 20551–20554.PubMedGoogle Scholar
  15. 15.
    Pollock DM, Opgenorth TJ. ETA receptor-mediated responses to endothelin-i and big endothelin-i in the rat kidney. Br J Pharmacol 1994; 111: 729–732.PubMedCrossRefGoogle Scholar
  16. 16.
    Davenport AP, O’Reilly G, Molenaar P et al. Human endothelin receptors characterized using reverse transcriptase-polymerase chain reaction, in situ hybridization, and subtype-selective ligands BQ-123 and BQ-3o2o: Evidence for expression of ETB receptors in human vascular smooth muscle. J Cardiovasc Pharmacol 1993; 22 (suppl. 8): S22 - S25.PubMedCrossRefGoogle Scholar
  17. 17.
    Shyamala V, Moulthrop TH, Stratton-Thomas J et al. Two distinct human endothelin B receptors generated by alternative splicing from a single gene. Cell Mol Biol Res 1994; 40: 285–296.PubMedGoogle Scholar
  18. 18.
    Cheng HF, Su YM, Yeh JR et al. Alternative transcript of the nonselective-type endothelin receptor from rat brain. Mol Pharmacol 1993; 44: 533–538.PubMedGoogle Scholar
  19. 19.
    Ihara M, Fukuroda TM, Saeki T et al. An endothelin receptor (ETA) antagonist isolated from streptomyces misakeienis. Biochem Biophys Res Comm 1991; 178: 132–137.PubMedCrossRefGoogle Scholar
  20. 20.
    Ishikawa K, Fukami T, Nagase T et al. Cyclic pentapeptide endothelin antagonists with high selectivity. Potency-and solubility-enhancing modifications. J Med Chem 1992; 35: 2139–2142.PubMedCrossRefGoogle Scholar
  21. 21.
    Sogabe K, Nirei H, Shoubo M et al. Pharmacological profile of FR139317, a novel, potent endothelin ETA receptor antagonist. J Pharmacol Exp Therap 1993; 264; 1040–1046.Google Scholar
  22. 22.
    Ishikawa K, Ihara M, Noguchi K et al. Biochemical and pharmacological profile of a potent and selective endothelin B-receptor antagonist, BQ-788. Proc Natl Acad Sci 1994; 91: 4892–4896.PubMedCrossRefGoogle Scholar
  23. 23.
    Cody WL Doherty AM, He JX et al. The rational design of a highly potent combined ETA and ETB receptor antagonist (PD 145065) and related analogs. Med Chem Res 1993; 3: 154–162.Google Scholar
  24. 24.
    Clozel M, Breu V, Burri K et al. Pathophysiological role of endothelin revealed by the first orally active endothelin receptor antagonist. Nature (London) 1993; 365: 759–761.CrossRefGoogle Scholar
  25. 25.
    Breu V, Loftier, B-M, Clozel M. In vitro characterization of Ro 46–2005, a novel synthetic nonpeptide endothelin antagonist of ETA and ETB receptors. FEBS Lett 1993; 334: 210.PubMedCrossRefGoogle Scholar
  26. 26.
    Clozel M, Breu V, Gray GA et al. Pharmacological characterization of bosentan, a new potent orally active nonpeptide endothelin receptor antagonist. J Pharmacol Exp Therap 1994; 270: 228–235.Google Scholar
  27. 27.
    Breu V, Clozel M, Burri K et al. In vitro characterization of Ro 46–8443, the first nonpeptide antagonist selective for the endothelin ETB receptor. FEBS Lett. 1996; 383: 37–41.PubMedCrossRefGoogle Scholar
  28. 28.
    Stein PD, Hunt JT, Floyd DM et al. The discovery of sulfonamide endothelin antagonists and the development of the orally active ETA antagonist 5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-napthalene-sulfonamide (BMS182874). J Med Chem 1994; 37: 329–331.PubMedCrossRefGoogle Scholar
  29. 29.
    Elliott JD, Lago AM, Cousins RD et al. 1,3-Diarylindan-2-carboxylic Acids: Potent and Selective Non-Peptide Endothelin Receptor Antagonists. J Med Chem 1994; 37: 1553–1557.PubMedCrossRefGoogle Scholar
  30. 30.
    Reynolds EE, Keiser JA, Haleen SJ et al. Pharmacological characterization of PD-156707, an orally-active ETA receptor antagonist. J Pharmacol Exp Therap 1995; 273: 1410–1417.Google Scholar
  31. 31.
    Winn M, von Geldern TW, Opgenorth TJ et al. 2,4-diarylpyrrolidine-3-carboxylic acids-Potent ETA selective endothelin receptor antagonists. i. Discovery of A-127722. J Med Chem. 1996; 39: 1039–1048.PubMedCrossRefGoogle Scholar
  32. 32.
    Jae HS, Winn M, Douglas B et al. Pyrrolidine-3-carboxylic acids as endothelin antagonists. 2. Sulfonamide-based ETA/ETB mixed antagonists. J Med Chem 1997; in press.Google Scholar
  33. 33.
    Miller VM, Komori K, Burnett Jr JC et al. Differential sensitivity to endothelin in canine arteries and veins. Am J Physiol 1989; 257: H1127 - H1131.PubMedGoogle Scholar
  34. 34.
    Moreland S, McMullen D, Abboa-Offei B et al. Evidence for a different location of vasoconstrictor endothelin receptors in the vasculature. Br J Pharmacol 1994; 112: 704–708.PubMedCrossRefGoogle Scholar
  35. 35.
    Plumpton C, Champeney R, Ashby MJ et al. Characterization of endothelin isoforms in human heart: endothelin-2 demonstrated. J Cardiovasc Pharmacol 1993; 22 (suppl. 8): S26 - S28.PubMedCrossRefGoogle Scholar
  36. 36.
    Molenaar P, O’Reilly G, Sharkey A et al. Characterization and localization of endothelin receptor subtypes in the human atrioventricular conducting system and myocardium. Circ Res 1993; 72: 526–538.PubMedCrossRefGoogle Scholar
  37. 37.
    Bax, WA, Bruinvels AT, van Suylen R-J et al. Endothelin receptors in the human coronary artery, ventricle and atrium. A quantitative autoradiographic analysis. Naunyn-Schmeid Arch Pharmacol 1993; 348: 403–410.Google Scholar
  38. 38.
    Davenport AP, Morton AJ, Brown MJ. Localization of endothelin-1 (ET-1), ET-2, and ET-3, mouse VIC, and sarafotoxin S6b binding sites in mammalian heart and kidney. J Cardiovasc Pharmacol 1991; 17 (suppl. 7): S152 - S155.PubMedCrossRefGoogle Scholar
  39. 39.
    Hemsen A, Franco-Cereceda A, Matran R et al. Occurrence, specific binding sites and functional effects of endothelin in human cardiopulmonary tissue. Eur J Pharmacol 1990; 191: 319–328.PubMedCrossRefGoogle Scholar
  40. 40.
    Thibault G, Doubell AF, Garcia R et al. Endothelin-stimulated secretion of natriuretic peptides by rat atrial myocytes is mediated by endothelin A receptors. Circ Res 1994; 74: 460–470.PubMedCrossRefGoogle Scholar
  41. 41.
    Williams Jr DL, Jones KL, Pettibone DJ et al. Sarafotoxin S6c: An agonist which distinguishes between endothelin receptor subtypes. Biochem Biophys Res Comm 1991; 175: 556–561.PubMedCrossRefGoogle Scholar
  42. 42.
    Bax WA, Aghai Z, van Tricht CLJ et al. Different endothelin receptors involved in endothelin-i-and sarafotoxjn S6B-induced contractions of the human isolated coronary artery. Br J Pharmacol 1994; 1131; 471–1479.Google Scholar
  43. 43.
    Godfraind T. Evidence for heterogeneity of endothelin receptor distribution in human coronary artery. Br J Pharmacol 1993; 110: 1201–1205.PubMedCrossRefGoogle Scholar
  44. 44.
    Opgaard OS, Adner M, Gulbenkian S et al. Localization of endothelin immunoreactivity and demonstration of constrictory endothelin-A receptors in human coronary arteries and veins. J Cardiovasc Pharmacol 1994; 23: 576–583.CrossRefGoogle Scholar
  45. 45.
    Davenport AP, Maguire JJ. Is endothelin-induced vasoconstriction mediated only by ETA receptors in humans? Trends Pharmacol Sci 1994; 15: 9–11.PubMedCrossRefGoogle Scholar
  46. 46.
    Davenport AP, O’Reilly G, Kuc RE. Endothelin ETA and ETB mRNA and receptors expressed by smooth muscle in the human vasculature: majority of the ETA subtype. Br J Pharmacol 1995; 114: 1110–1116.PubMedCrossRefGoogle Scholar
  47. 47.
    Karet FE, Kuc RE, Davenport AP. Novel ligands BQ-123 and BQ-3o2o characterize endothelin receptor subtypes ETA and ETB in human kidney. Kidney Int 1993; 44: 36–42.PubMedCrossRefGoogle Scholar
  48. 48.
    Kitamura K, Tanaka T, Kato J et al. Immunoreactive endothelin in rat kidney inner medulla: marked decrease in spontaneously hypertensive rats. Biochem Biophys Res Comm 1989; 162: 38–44.PubMedCrossRefGoogle Scholar
  49. 49.
    Morita S, Kitamura K, Yamamoto Y et al. Immunoreactive endothelin in human kidney. Ann Clin Biochem 1991; 28: 267–271.PubMedGoogle Scholar
  50. 50.
    Wilkes BM, Susin M, Mento PF et al. Localization of endothelin-like immunoreactivity in rat kidneys. Am J Physiol 1991; 260: F913 - F92o.PubMedGoogle Scholar
  51. 51.
    Chen M, Todd-Turla K, Wang W-H et al. Endothelin-1 mRNA in glomerular and epithelial cells of kidney. Am J Physiol 1993; 265: F542 - F55o.PubMedGoogle Scholar
  52. 52.
    Pupilla C, Brunori M, Misciglia N et al. Presence and distribution of endothelin-i gene expression in human kidney. Am J Physiol 1994; 267: F679 - F687.Google Scholar
  53. 53.
    Jones CR, Hiley CR, Pelton JT et al. Autoradiographic localization of endothelin binding sites in kidney. Eur J Pharmacol 1989; 163: 379–382.PubMedCrossRefGoogle Scholar
  54. 54.
    Kohzuki M, Johnson CI, Chai SY et al. Localization of endothelin receptors in rat kidney. Eur J Pharmacol 1989; 160: 193–194.PubMedCrossRefGoogle Scholar
  55. 55.
    Neuser D, Zaiss S, Stasch JP. Endothelin receptors in cultured renal epithelial cells. Eur J Pharmacol 1990; 176: 241–243.PubMedCrossRefGoogle Scholar
  56. 56.
    Matsumoto H, Suzuki N, Onda H et al. Abundance of endothelin-3 in rat intestine, pituitary gland, and brain. Biochem Biophys Res Comm 1989; 164: 74–80.PubMedCrossRefGoogle Scholar
  57. 57.
    Rosengurt N, Springall D, Polak J. Localization of endothelin-like immunoreactivity in airway epithelia of rats and mice. J Pathol 1990; 160: 5–8.CrossRefGoogle Scholar
  58. 58.
    Marciniak SJ, Plumpton C, Barker PJ et al. Localization of immunoreactive endothelin and proendothelin in the human lung. Pulm Pharmacol 1992; 5: 175–182.PubMedCrossRefGoogle Scholar
  59. 59.
    Giaid A, Polak JM, Gaitonde V et al. Distribution of endothelin-like immunoreactivity and mRNA in the developing and adult human lung. Am J Respir Cell Mol Biol 1991; 4: 50–58.PubMedGoogle Scholar
  60. 6o.
    Fukuroda T, Kobayashi M, Ozaki S et al. Endothelin receptor subtypes in human versus rabbit pulmonary arteries. J Appl Physiol 1994; 76: 1976–1982.PubMedGoogle Scholar
  61. 61.
    Knott PG, D’Aprile AC, Henry PJ et al. Receptors for endothelin-i in asthmatic human peripheral lung. Br J Pharmacol 1995; 114: 1–3.PubMedCrossRefGoogle Scholar
  62. 62.
    Horgan MJ, Pinheiro JMB, Malik AB. Mechanism of endothelin-i-induced pulmonary vasoconstriction. Circ Res 1991; 69: 157–164.PubMedCrossRefGoogle Scholar
  63. 63.
    Brink C, Gillard V, Roubert P et al. Effects of specific binding sites of endothelin in human lung preparations. Pulm Pharmacol 1991; 4: 54–59.PubMedCrossRefGoogle Scholar
  64. 64.
    Toga H, Ibe BO, Raj JU. In vitro responses of ovine intrapulmonary arteries and veins to endothelin-i. Am J Physiol 1992; 263: L15 - L21.PubMedGoogle Scholar
  65. 65.
    Lee ME, de la Monte SM, Ng S-C et al. Expression of the potent vasoconstrictor endothelin in human central nervous system. J Clin Invest 1990; 86: 141–147.PubMedCrossRefGoogle Scholar
  66. 66.
    Yoshizawa T, Shinmi O, Giaid A et al. Endothelin: a novel peptide in posterior pituitary system. Science 1990; 247: 462–464.PubMedCrossRefGoogle Scholar
  67. 67.
    MacCumber MW, Ross CA, Snyder SH. Endothelin in brain: receptors, mitogenesis, and biosynthesis in glial cells. Proc Natl Acad Sci 1990; 87: 2359–2363.PubMedCrossRefGoogle Scholar
  68. 68.
    Giaid A, Bibson SJ, Ibrahim BN et al. Endothelin 1, an endothelium derived peptide, is expressed in neurons of the human spinal cord and dorsal root ganglia. Proc Natl Acad Sci 1989; 86: 7634–7638.PubMedCrossRefGoogle Scholar
  69. 69.
    Kobayashi M, Ihara M, Sato N et al. A novel ligand, [125I]BQ-3o2o, reveals the localization of endothelin ETB receptors. Eur J Pharmacol 1993; 235: 95–100.PubMedCrossRefGoogle Scholar
  70. 70.
    Elshourbagy MA, Lee JA, Korman DR et al. Molecular cloning and characterization of the major endothelin receptor subtype in porcine cerebellum. Mol Pharmacol 1992; 41: 465–473.PubMedGoogle Scholar
  71. 71.
    De Olivera AM, Viswanathan M, Capsoni S et al. Characterization of endothelin A receptors in cerebral and peripheral arteries of the rat. Peptides 1995; 16: 139–144.CrossRefGoogle Scholar
  72. 72.
    Sagher O, Jim Y, Thai QA et al. Cerebral microvascular responses to endothelins: the role of ETA receptors. Brain Res 1994; 658: 179 - i84.PubMedCrossRefGoogle Scholar
  73. 73.
    Vigne P, Breittmayer JP, Felin C. Competitive and noncompetitive interactions of BQ-123 with endothelin ETA receptors. Eur J Pharmacol 1993; 245: 229–232.PubMedCrossRefGoogle Scholar
  74. 74.
    Stanimirovic DB, Yamamoto T, Uematsu S et al. Endothelin-1 receptor binding and cellular signal transduction in cultured human brain endothelial cells. J Neurochem 1994; 62: 592–601.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Andrew S. Tasker
  • David M. Pollock

There are no affiliations available

Personalised recommendations