• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of brjpharmLink to Publisher's site
Br J Pharmacol. Mar 1995; 114(6): 1110–1116.
PMCID: PMC1510347

Endothelin ETA and ETB mRNA and receptors expressed by smooth muscle in the human vasculature: majority of the ETA sub-type.

Abstract

1. We measured the ratio of ETA and ETB sub-types in the media (containing mainly smooth muscle) of human cardiac arteries (aorta, pulmonary and coronary), internal mammary arteries and saphenous veins. 2. In saturation experiments, [125I]-endothelin-1 ([125I]-ET-1) bound with high affinity to the media of each vessel (n = 3 individuals or homogenate preparations +/- s.e. mean): coronary artery, KD = 0.14 +/- 0.02 nM, Bmax = 71.0 +/- 21.0 fmol mg-1 protein; pulmonary artery, KD = 0.85 +/- 0.25 nM, Bmax = 15.2 +/- 10.3 fmol mg-1 protein; aorta, KD = 0.51 +/- 0.02 nM, Bmax = 9.4 +/- 4.4 fmol mg-1 protein; internal mammary artery. KD = 0.34 +/- 0.31 nM, Bmax = 2.0 +/- 0.5 fmol mg-1 protein and saphenous vein, KD = 0.28 +/- 0.05 nM, Bmax = 52.8 +/- 1.0 fmol mg-1 protein. In each vessel, over the concentration-range tested, Hill slopes were close to unity and a one site fit was preferred to a two site model. 3. In competition binding assays, the ETA selective ligand, BQ123 inhibited the binding of 0.1 nM [125I]-ET-1 to the media in a biphasic manner. In each case, a two site fit was preferred to a one or three site model: coronary artery, KDETA = 0.85 +/- 0.03 nM, KDETB = 7.58 +/- 2.27 microM, ratio = 89:11%; pulmonary artery, KDETA = 0.27 +/- 0.05 nM, KDETB = 24.60 +/- 5.34 microM, ratio = 92:8%; aorta, KDETA = 0.80 +/- 0.40 nM, KDETB = 2.67 +/- 2.60 microM ratio = 89:11%; saphenous vein, KDETA = 0.55 +/- 0.17 nM, KDETB = 14.4 +/- 0.26 microM, 85:15% (n = 3 individuals or homogenate preparations +/- s.e. mean). BQ123 showed up to 18000 fold selectivity for the ETA over the ETB sub-type. The ETA-selective ligand, [125I]-PD151242 labelled 85% of the receptors detected by a fixed concentration of [125I]-ET-1 in media of internal mammary artery, measured by quantitative autoradiography. In contrast, the density of ETB receptors detected with [125I]-BQ3020 was 7.0 +/- 1.5 amol mm-2, representing about 8% of [125I]-ET-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Akar F, Uydes BS, Ayrancioğlu K, Yener A, Aşlamaci S, Arsan M, Törüner A, Kanzik I. Endothelial function of human gastroepiploic artery in comparison with saphenous vein. Cardiovasc Res. 1994 Apr;28(4):500–504. [PubMed]
  • Bax WA, Bruinvels AT, van Suylen RJ, Saxena PR, Hoyer D. Endothelin receptors in the human coronary artery, ventricle and atrium. A quantitative autoradiographic analysis. Naunyn Schmiedebergs Arch Pharmacol. 1993 Oct;348(4):403–410. [PubMed]
  • Bigaud M, Pelton JT. Discrimination between ETA- and ETB-receptor-mediated effects of endothelin-1 and [Ala1,3,11,15]endothelin-1 by BQ-123 in the anaesthetized rat. Br J Pharmacol. 1992 Dec;107(4):912–918. [PMC free article] [PubMed]
  • Bodelsson G, Stjernquist M. Characterization of endothelin receptors and localization of 125I-endothelin-1 binding sites in human umbilical artery. Eur J Pharmacol. 1993 Nov 16;249(3):299–305. [PubMed]
  • Clozel M, Gray GA, Breu V, Löffler BM, Osterwalder R. The endothelin ETB receptor mediates both vasodilation and vasoconstriction in vivo. Biochem Biophys Res Commun. 1992 Jul 31;186(2):867–873. [PubMed]
  • Costello KB, Stewart DJ, Baffour R. Endothelin is a potent constrictor of human vessels used in coronary revascularization surgery. Eur J Pharmacol. 1990 Sep 21;186(2-3):311–314. [PubMed]
  • Cristol JP, Warner TD, Thiemermann C, Vane JR. 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 Mar;108(3):776–779. [PMC free article] [PubMed]
  • Davenport AP, Kuc RE, Hoskins SL, Karet FE, Fitzgerald F. [125I]-PD151242: a selective ligand for endothelin ETA receptors in human kidney which localizes to renal vasculature. Br J Pharmacol. 1994 Dec;113(4):1303–1310. [PMC free article] [PubMed]
  • Davenport AP, Maguire JJ. Is endothelin-induced vasoconstriction mediated only by ETA receptors in humans? Trends Pharmacol Sci. 1994 Jan;15(1):9–11. [PubMed]
  • 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. [PubMed]
  • Davenport AP, Nunez DJ, Brown MJ. Binding sites for 125I-labelled endothelin-1 in the kidneys: differential distribution in rat, pig and man demonstrated by using quantitative autoradiography. Clin Sci (Lond) 1989 Aug;77(2):129–131. [PubMed]
  • Davenport AP, Nunez DJ, Hall JA, Kaumann AJ, Brown MJ. Autoradiographical localization of binding sites for porcine [125I]endothelin-1 in humans, pigs, and rats: functional relevance in humans. J Cardiovasc Pharmacol. 1989;13 (Suppl 5):S166–S170. [PubMed]
  • Grossman E, Rosenthal T, Peleg E, Holmes C, Goldstein DS. Oral yohimbine increases blood pressure and sympathetic nervous outflow in hypertensive patients. J Cardiovasc Pharmacol. 1993 Jul;22(1):22–26. [PubMed]
  • Franco-Cereceda A. Endothelin- and neuropeptide Y-induced vasoconstriction of human epicardial coronary arteries in vitro. Br J Pharmacol. 1989 Jul;97(3):968–972. [PMC free article] [PubMed]
  • Fukuroda T, Kobayashi M, Ozaki S, Yano M, Miyauchi T, Onizuka M, Sugishita Y, Goto K, Nishikibe M. Endothelin receptor subtypes in human versus rabbit pulmonary arteries. J Appl Physiol (1985) 1994 May;76(5):1976–1982. [PubMed]
  • Gardiner SM, Kemp PA, March JE, Bennett T, Davenport AP, Edvinsson L. Effects of an ET1-receptor antagonist, FR139317, on regional haemodynamic responses to endothelin-1 and [Ala11,15]Ac-endothelin-1 (6-21) in conscious rats. Br J Pharmacol. 1994 Jun;112(2):477–486. [PMC free article] [PubMed]
  • Godfraind T. Evidence for heterogeneity of endothelin receptor distribution in human coronary artery. Br J Pharmacol. 1993 Nov;110(3):1201–1205. [PMC free article] [PubMed]
  • Hay DW, Luttmann MA, Hubbard WC, Undem BJ. Endothelin receptor subtypes in human and guinea-pig pulmonary tissues. Br J Pharmacol. 1993 Nov;110(3):1175–1183. [PMC free article] [PubMed]
  • Howard PG, Plumpton C, Davenport AP. Anatomical localization and pharmacological activity of mature endothelins and their precursors in human vascular tissue. J Hypertens. 1992 Nov;10(11):1379–1386. [PubMed]
  • Ihara M, Noguchi K, Saeki T, Fukuroda T, Tsuchida S, Kimura S, Fukami T, Ishikawa K, Nishikibe M, Yano M. Biological profiles of highly potent novel endothelin antagonists selective for the ETA receptor. Life Sci. 1992;50(4):247–255. [PubMed]
  • Karet FE, Charnock-Jones DS, Harrison-Woolrych ML, O'Reilly G, Davenport AP, Smith SK. Quantification of mRNA in human tissue using fluorescent nested reverse-transcriptase polymerase chain reaction. Anal Biochem. 1994 Aug 1;220(2):384–390. [PubMed]
  • Karet FE, Kuc RE, Davenport AP. Novel ligands BQ123 and BQ3020 characterize endothelin receptor subtypes ETA and ETB in human kidney. Kidney Int. 1993 Jul;44(1):36–42. [PubMed]
  • Lüscher TF, Yang Z, Tschudi M, von Segesser L, Stulz P, Boulanger C, Siebenmann R, Turina M, Bühler FR. Interaction between endothelin-1 and endothelium-derived relaxing factor in human arteries and veins. Circ Res. 1990 Apr;66(4):1088–1094. [PubMed]
  • Maguire JJ, Bacon CR, Fujimoto M, Davenport AP. Myricerone caffeoyl ester (50-235) is a non-peptide antagonist selective for human ETA receptors. J Hypertens. 1994 Jun;12(6):675–680. [PubMed]
  • Maguire JJ, Kuc RE, O'Reilly G, Davenport AP. Vasoconstrictor endothelin receptors characterized in human renal artery and vein in vitro. Br J Pharmacol. 1994 Sep;113(1):49–54. [PMC free article] [PubMed]
  • Molenaar P, Kuc RE, Davenport AP. Characterization of two new ETB selective radioligands, [125I]-BQ3020 and [125I]-[Ala1,3,11,15]ET-1 in human heart. Br J Pharmacol. 1992 Nov;107(3):637–639. [PMC free article] [PubMed]
  • Molenaar P, O'Reilly G, Sharkey A, Kuc RE, Harding DP, Plumpton C, Gresham GA, Davenport AP. Characterization and localization of endothelin receptor subtypes in the human atrioventricular conducting system and myocardium. Circ Res. 1993 Mar;72(3):526–538. [PubMed]
  • Saetrum Opgaard O, Adner M, Gulbenkian S, Edvinsson L. Localization of endothelin immunoreactivity and demonstration of constrictory endothelin-A receptors in human coronary arteries and veins. J Cardiovasc Pharmacol. 1994 Apr;23(4):576–583. [PubMed]
  • O'Reilly G, Charnock-Jones DS, Davenport AP, Cameron IT, Smith SK. Presence of messenger ribonucleic acid for endothelin-1, endothelin-2, and endothelin-3 in human endometrium and a change in the ratio of ETA and ETB receptor subtype across the menstrual cycle. J Clin Endocrinol Metab. 1992 Dec;75(6):1545–1549. [PubMed]
  • O'Reilly G, Charnock-Jones DS, Morrison JJ, Cameron IT, Davenport AP, Smith SK. Alternatively spliced mRNAs for human endothelin-2 and their tissue distribution. Biochem Biophys Res Commun. 1993 Jun 30;193(3):834–840. [PubMed]
  • Peter MG, Davenport AP. Selectivity of [125I]-PD151242 for human, rat and porcine endothelin ETA receptors in the heart. Br J Pharmacol. 1995 Jan;114(2):297–302. [PMC free article] [PubMed]
  • Pollock DM, Opgenorth TJ. Evidence for endothelin-induced renal vasoconstriction independent of ETA receptor activation. Am J Physiol. 1993 Jan;264(1 Pt 2):R222–R226. [PubMed]
  • Pollock DM, Opgenorth TJ. ETA receptor-mediated responses to endothelin-1 and big endothelin-1 in the rat kidney. Br J Pharmacol. 1994 Mar;111(3):729–732. [PMC free article] [PubMed]
  • Riezebos J, Watts IS, Vallance PJ. Endothelin receptors mediating functional responses in human small arteries and veins. Br J Pharmacol. 1994 Feb;111(2):609–615. [PMC free article] [PubMed]
  • Robaut C, Mondon F, Bandet J, Ferre F, Cavero I. Regional distribution and pharmacological characterization of [125I]endothelin-1 binding sites in human fetal placental vessels. Placenta. 1991 Jan-Feb;12(1):55–67. [PubMed]
  • Seo B, Oemar BS, Siebenmann R, von Segesser L, Lüscher TF. Both ETA and ETB receptors mediate contraction to endothelin-1 in human blood vessels. Circulation. 1994 Mar;89(3):1203–1208. [PubMed]
  • Sumner MJ, Cannon TR, Mundin JW, White DG, Watts IS. Endothelin ETA and ETB receptors mediate vascular smooth muscle contraction. Br J Pharmacol. 1992 Nov;107(3):858–860. [PMC free article] [PubMed]
  • Télémaque S, Gratton JP, Claing A, D'Orléans-Juste P. Endothelin-1 induces vasoconstriction and prostacyclin release via the activation of endothelin ETA receptors in the perfused rabbit kidney. Eur J Pharmacol. 1993 Jun 24;237(2-3):275–281. [PubMed]
  • Wellings RP, Corder R, Warner TD, Cristol JP, Thiemermann C, Vane JR. Evidence from receptor antagonists of an important role for ETB receptor-mediated vasoconstrictor effects of endothelin-1 in the rat kidney. Br J Pharmacol. 1994 Feb;111(2):515–520. [PMC free article] [PubMed]
  • White DG, Cannon TR, Garratt H, Mundin JW, Sumner MJ, Watts IS. Endothelin ETA and ETB receptors mediate vascular smooth-muscle contraction. J Cardiovasc Pharmacol. 1993;22 (Suppl 8):S144–S148. [PubMed]
  • White DG, Garratt H, Mundin JW, Sumner MJ, Vallance PJ, Watts IS. Human saphenous vein contains both endothelin ETA and ETB contractile receptors. Eur J Pharmacol. 1994 May 23;257(3):307–310. [PubMed]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...