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. 1993 Jun;109(2):544–552. doi: 10.1111/j.1476-5381.1993.tb13605.x

Differential localization of endothelin ETA and ETB binding sites in human placenta.

R A Rutherford 1, J Wharton 1, A McCarthy 1, L Gordon 1, M H Sullivan 1, M G Elder 1, J M Polak 1
PMCID: PMC2175708  PMID: 8358555

Abstract

1. The localization and differential distribution of endothelin (ET) receptor subtypes (ETA and ETB) was investigated in sections of human placenta by use of quantitative in vitro autoradiography and receptor selective ligands. 2. Specific, high density [125I]-ET-1 binding sites were localized to the decidua and foetal membranes as well as to arteries and veins in the chorionic plate and throughout the villous tree. Moderate to low density binding was found in the extravillous and villous trophoblast respectively. 3. [125I]-ET-1 binding sites exhibited a rank order of inhibition by unlabelled peptide sequences (ET-1 > ET-3 > [Ala3,11,18Nle7]-ET-1 > BQ123 > or = sarafotoxin 6c). However, in contrast to the monophasic inhibition curve of ET-1, the other sequences produced a significantly better fit to a two component inhibition curve suggesting the presence of a heterogeneous population of ET binding sites. 4. ETA and ETB receptors were distinguished by competitive inhibition of [125]-ET-1 binding with increasing concentrations of unlabelled ET-3, [Ala3,11,18Nle7]-ET-1, sarafotoxin 6c and BQ123 and by incubating sections with the ETB agonist, [125I]-BQ3020. ET receptor subtypes exhibited a differential distribution in the placenta. ETA type binding sites predominated (approximately 80% of the total) on veins and arteries in the chorionic plate. Veins in stem villi, blood vessels in distal regions of the villous tree and decidual cells displayed a high density (approximately 60-70% of the total) of the ETB receptor subtype.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adachi M., Yang Y. Y., Furuichi Y., Miyamoto C. Cloning and characterization of cDNA encoding human A-type endothelin receptor. Biochem Biophys Res Commun. 1991 Nov 14;180(3):1265–1272. doi: 10.1016/s0006-291x(05)81332-4. [DOI] [PubMed] [Google Scholar]
  2. Aramori I., Nakanishi S. Coupling of two endothelin receptor subtypes to differing signal transduction in transfected Chinese hamster ovary cells. J Biol Chem. 1992 Jun 25;267(18):12468–12474. [PubMed] [Google Scholar]
  3. Benigni A., Gaspari F., Orisio S., Bellizzi L., Amuso G., Frusca T., Remuzzi G. Human placenta expresses endothelin gene and corresponding protein is excreted in urine in increasing amounts during normal pregnancy. Am J Obstet Gynecol. 1991 Mar;164(3):844–848. doi: 10.1016/0002-9378(91)90527-x. [DOI] [PubMed] [Google Scholar]
  4. Benigni A., Orisio S., Gaspari F., Frusca T., Amuso G., Remuzzi G. Evidence against a pathogenetic role for endothelin in pre-eclampsia. Br J Obstet Gynaecol. 1992 Oct;99(10):798–802. doi: 10.1111/j.1471-0528.1992.tb14409.x. [DOI] [PubMed] [Google Scholar]
  5. Cameron I. T., Davenport A. P., Brown M. J., Smith S. K. Endothelin-1 stimulates prostaglandin F2 alpha release from human endometrium. Prostaglandins Leukot Essent Fatty Acids. 1991 Mar;42(3):155–157. doi: 10.1016/0952-3278(91)90150-4. [DOI] [PubMed] [Google Scholar]
  6. Clark B. A., Halvorson L., Sachs B., Epstein F. H. Plasma endothelin levels in preeclampsia: elevation and correlation with uric acid levels and renal impairment. Am J Obstet Gynecol. 1992 Mar;166(3):962–968. doi: 10.1016/0002-9378(92)91372-h. [DOI] [PubMed] [Google Scholar]
  7. Fant M. E., Nanu L., Word R. A. A potential role for endothelin-1 in human placental growth: interactions with the insulin-like growth factor family of peptides. J Clin Endocrinol Metab. 1992 May;74(5):1158–1163. doi: 10.1210/jcem.74.5.1373736. [DOI] [PubMed] [Google Scholar]
  8. Fischli W., Clozel M., Guilly C. Specific receptors for endothelin on membranes from human placenta. Characterization and use in a binding assay. Life Sci. 1989;44(20):1429–1436. doi: 10.1016/0024-3205(89)90321-4. [DOI] [PubMed] [Google Scholar]
  9. Fukuroda T., Nishikibe M., Ohta Y., Ihara M., Yano M., Ishikawa K., Fukami T., Ikemoto F. Analysis of responses to endothelins in isolated porcine blood vessels by using a novel endothelin antagonist, BQ-153. Life Sci. 1992;50(15):PL107–PL112. doi: 10.1016/0024-3205(92)90353-q. [DOI] [PubMed] [Google Scholar]
  10. Hemsén A., Gillis C., Larsson O., Haegerstrand A., Lundberg J. M. Characterization, localization and actions of endothelins in umbilical vessels and placenta of man. Acta Physiol Scand. 1991 Dec;143(4):395–404. doi: 10.1111/j.1748-1716.1991.tb09251.x. [DOI] [PubMed] [Google Scholar]
  11. Howard R. B. Control of human placental blood flow. Med Hypotheses. 1987 May;23(1):51–58. doi: 10.1016/0306-9877(87)90180-0. [DOI] [PubMed] [Google Scholar]
  12. Hu J. R., Berninger U. G., Lang R. E. Endothelin stimulates atrial natriuretic peptide (ANP) release from rat atria. Eur J Pharmacol. 1988 Dec 6;158(1-2):177–178. doi: 10.1016/0014-2999(88)90271-3. [DOI] [PubMed] [Google Scholar]
  13. 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. doi: 10.1016/0024-3205(92)90331-i. [DOI] [PubMed] [Google Scholar]
  14. Ihara M., Saeki T., Fukuroda T., Kimura S., Ozaki S., Patel A. C., Yano M. A novel radioligand [125I]BQ-3020 selective for endothelin (ETB) receptors. Life Sci. 1992;51(6):PL47–PL52. doi: 10.1016/0024-3205(92)90418-o. [DOI] [PubMed] [Google Scholar]
  15. Kohno M., Yasunari K., Yokokawa K., Murakawa K., Horio T., Takeda T. Inhibition by atrial and brain natriuretic peptides of endothelin-1 secretion after stimulation with angiotensin II and thrombin of cultured human endothelial cells. J Clin Invest. 1991 Jun;87(6):1999–2004. doi: 10.1172/JCI115228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. MacLean M. R., Templeton A. G., McGrath J. C. The influence of endothelin-1 on human foeto-placental blood vessels: a comparison with 5-hydroxytryptamine. Br J Pharmacol. 1992 Aug;106(4):937–941. doi: 10.1111/j.1476-5381.1992.tb14438.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Malee M. P., Malee K. M., Azuma S. D., Taylor R. N., Roberts J. M. Increases in plasma atrial natriuretic peptide concentration antedate clinical evidence of preeclampsia. J Clin Endocrinol Metab. 1992 May;74(5):1095–1100. doi: 10.1210/jcem.74.5.1533228. [DOI] [PubMed] [Google Scholar]
  18. Mastrogiannis D. S., O'Brien W. F., Krammer J., Benoit R. Potential role of endothelin-1 in normal and hypertensive pregnancies. Am J Obstet Gynecol. 1991 Dec;165(6 Pt 1):1711–1716. doi: 10.1016/0002-9378(91)90020-r. [DOI] [PubMed] [Google Scholar]
  19. Mattoli S., Soloperto M., Mezzetti M., Fasoli A. Mechanisms of calcium mobilization and phosphoinositide hydrolysis in human bronchial smooth muscle cells by endothelin 1. Am J Respir Cell Mol Biol. 1991 Nov;5(5):424–430. doi: 10.1165/ajrcmb/5.5.424. [DOI] [PubMed] [Google Scholar]
  20. McQueen J., Jardine A., Kingdom J., Templeton A., Whittle M. J., Connell J. M. Interaction of angiotensin II and atrial natriuretic peptide in the human fetoplacental unit. Am J Hypertens. 1990 Aug;3(8 Pt 1):641–644. doi: 10.1093/ajh/3.8.641. [DOI] [PubMed] [Google Scholar]
  21. McQueen J., Kingdom J. C., Jardine A. G., Connell J. M., Whittle M. J. Vascular angiotensin II and atrial natriuretic peptide receptors in normal and growth-retarded human placentae. J Endocrinol. 1990 Aug;126(2):341–347. doi: 10.1677/joe.0.1260341. [DOI] [PubMed] [Google Scholar]
  22. Moreland S., McMullen D. M., Delaney C. L., Lee V. G., Hunt J. T. Venous smooth muscle contains vasoconstrictor ETB-like receptors. Biochem Biophys Res Commun. 1992 Apr 15;184(1):100–106. doi: 10.1016/0006-291x(92)91163-k. [DOI] [PubMed] [Google Scholar]
  23. Nakajo S., Sugiura M., Snajdar R. M., Boehm F. H., Inagami T. Solubilization and identification of human placental endothelin receptor. Biochem Biophys Res Commun. 1989 Oct 16;164(1):205–211. doi: 10.1016/0006-291x(89)91703-8. [DOI] [PubMed] [Google Scholar]
  24. Nakamichi K., Ihara M., Kobayashi M., Saeki T., Ishikawa K., Yano M. Different distribution of endothelin receptor subtypes in pulmonary tissues revealed by the novel selective ligands BQ-123 and [Ala1,3,11,15]ET-1. Biochem Biophys Res Commun. 1992 Jan 15;182(1):144–150. doi: 10.1016/s0006-291x(05)80123-8. [DOI] [PubMed] [Google Scholar]
  25. Namiki A., Hirata Y., Ishikawa M., Moroi M., Aikawa J., Machii K. Endothelin-1- and endothelin-3-induced vasorelaxation via common generation of endothelium-derived nitric oxide. Life Sci. 1992;50(10):677–682. doi: 10.1016/0024-3205(92)90470-a. [DOI] [PubMed] [Google Scholar]
  26. Nova A., Sibai B. M., Barton J. R., Mercer B. M., Mitchell M. D. Maternal plasma level of endothelin is increased in preeclampsia. Am J Obstet Gynecol. 1991 Sep;165(3):724–727. doi: 10.1016/0002-9378(91)90317-k. [DOI] [PubMed] [Google Scholar]
  27. Ogawa Y., Nakao K., Arai H., Nakagawa O., Hosoda K., Suga S., Nakanishi S., Imura H. Molecular cloning of a non-isopeptide-selective human endothelin receptor. Biochem Biophys Res Commun. 1991 Jul 15;178(1):248–255. doi: 10.1016/0006-291x(91)91806-n. [DOI] [PubMed] [Google Scholar]
  28. Onda H., Ohkubo S., Ogi K., Kosaka T., Kimura C., Matsumoto H., Suzuki N., Fujino M. One of the endothelin gene family, endothelin 3 gene, is expressed in the placenta. FEBS Lett. 1990 Feb 26;261(2):327–330. doi: 10.1016/0014-5793(90)80583-5. [DOI] [PubMed] [Google Scholar]
  29. Otani S., Usuki S., Saitoh T., Yanagisawa M., Iwasaki H., Tanaka J., Suzuki N., Fujino M., Goto K., Masaki T. Comparison of endothelin-1 concentrations in normal and complicated pregnancies. J Cardiovasc Pharmacol. 1991;17 (Suppl 7):S308–S312. doi: 10.1097/00005344-199100177-00088. [DOI] [PubMed] [Google Scholar]
  30. Panek R. L., Major T. C., Hingorani G. P., Doherty A. M., Taylor D. G., Rapundalo S. T. Endothelin and structurally related analogs distinguish between endothelin receptor subtypes. Biochem Biophys Res Commun. 1992 Mar 16;183(2):566–571. doi: 10.1016/0006-291x(92)90519-q. [DOI] [PubMed] [Google Scholar]
  31. Rae G. A., Trybulec M., de Nucci G., Vane J. R. Endothelin-1 releases eicosanoids from rabbit isolated perfused kidney and spleen. J Cardiovasc Pharmacol. 1989;13 (Suppl 5):S89–S102. doi: 10.1097/00005344-198900135-00022. [DOI] [PubMed] [Google Scholar]
  32. Reilly F. D., Russell P. T. Neurohistochemical evidence supporting an absence of adrenergic and cholinergic innervation in the human placenta and umbilical cord. Anat Rec. 1977 Jul;188(3):277–286. doi: 10.1002/ar.1091880302. [DOI] [PubMed] [Google Scholar]
  33. 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. doi: 10.1016/0143-4004(91)90510-m. [DOI] [PubMed] [Google Scholar]
  34. Saeki T., Ihara M., Fukuroda T., Yamagiwa M., Yano M. [Ala1,3,11,15]endothelin-1 analogs with ETB agonistic activity. Biochem Biophys Res Commun. 1991 Aug 30;179(1):286–292. doi: 10.1016/0006-291x(91)91367-l. [DOI] [PubMed] [Google Scholar]
  35. Salas S. P., Power R. F., Singleton A., Wharton J., Polak J. M., Brown J. Heterogeneous binding sites for alpha-atrial natriuretic peptide in human umbilical cord and placenta. Am J Physiol. 1991 Sep;261(3 Pt 2):R633–R638. doi: 10.1152/ajpregu.1991.261.3.R633. [DOI] [PubMed] [Google Scholar]
  36. Sokolovsky M. Endothelins and sarafotoxins: physiological regulation, receptor subtypes and transmembrane signaling. Trends Biochem Sci. 1991 Jul;16(7):261–264. doi: 10.1016/0968-0004(91)90100-a. [DOI] [PubMed] [Google Scholar]
  37. Takayanagi R., Kitazumi K., Takasaki C., Ohnaka K., Aimoto S., Tasaka K., Ohashi M., Nawata H. Presence of non-selective type of endothelin receptor on vascular endothelium and its linkage to vasodilation. FEBS Lett. 1991 Apr 22;282(1):103–106. doi: 10.1016/0014-5793(91)80454-b. [DOI] [PubMed] [Google Scholar]
  38. Vijayaraghavan J., Scicli A. G., Carretero O. A., Slaughter C., Moomaw C., Hersh L. B. The hydrolysis of endothelins by neutral endopeptidase 24.11 (enkephalinase). J Biol Chem. 1990 Aug 25;265(24):14150–14155. [PubMed] [Google Scholar]
  39. Wada K., Tabuchi H., Ohba R., Satoh M., Tachibana Y., Akiyama N., Hiraoka O., Asakura A., Miyamoto C., Furuichi Y. Purification of an endothelin receptor from human placenta. Biochem Biophys Res Commun. 1990 Feb 28;167(1):251–257. doi: 10.1016/0006-291x(90)91758-k. [DOI] [PubMed] [Google Scholar]
  40. Wallenstein S., Zucker C. L., Fleiss J. L. Some statistical methods useful in circulation research. Circ Res. 1980 Jul;47(1):1–9. doi: 10.1161/01.res.47.1.1. [DOI] [PubMed] [Google Scholar]
  41. Wharton J., Rutherford R. A., Gordon L., Moscoso G., Schiemberg I., Gaer J. A., Taylor K. M., Polak J. M. Localization of endothelin binding sites and endothelin-like immunoreactivity in human fetal heart. J Cardiovasc Pharmacol. 1991;17 (Suppl 7):S378–S384. doi: 10.1097/00005344-199100177-00107. [DOI] [PubMed] [Google Scholar]
  42. Wilkes B. M., Mento P. F., Hollander A. M., Maita M. E., Sung S., Girardi E. P. Endothelin receptors in human placenta: relationship to vascular resistance and thromboxane release. Am J Physiol. 1990 May;258(5 Pt 1):E864–E870. doi: 10.1152/ajpendo.1990.258.5.E864. [DOI] [PubMed] [Google Scholar]
  43. Williams D. L., Jr, Jones K. L., Pettibone D. J., Lis E. V., Clineschmidt B. V. Sarafotoxin S6c: an agonist which distinguishes between endothelin receptor subtypes. Biochem Biophys Res Commun. 1991 Mar 15;175(2):556–561. doi: 10.1016/0006-291x(91)91601-8. [DOI] [PubMed] [Google Scholar]
  44. de Nucci G., Thomas R., D'Orleans-Juste P., Antunes E., Walder C., Warner T. D., Vane J. R. Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyclin and endothelium-derived relaxing factor. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9797–9800. doi: 10.1073/pnas.85.24.9797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. van Papendorp C. L., Cameron I. T., Davenport A. P., King A., Barker P. J., Huskisson N. S., Gilmour R. S., Brown M. J., Smith S. K. Localization and endogenous concentration of endothelin-like immunoreactivity in human placenta. J Endocrinol. 1991 Dec;131(3):507–511. doi: 10.1677/joe.0.1310507. [DOI] [PubMed] [Google Scholar]

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