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. 1994 Apr;111(4):1009–1016. doi: 10.1111/j.1476-5381.1994.tb14844.x

Characterization of ETB receptors mediating contractions induced by endothelin-1 or IRL 1620 in guinea-pig isolated airways: effects of BQ-123, FR139317 or PD 145065.

B Battistini 1, T D Warner 1, A Fournier 1, J R Vane 1
PMCID: PMC1910170  PMID: 8032583

Abstract

1. We have characterized the receptors mediating contractions to endothelin-1 (ET-1) or IRL 1620, an ETB receptor selective agonist, in isolated strips of tissue prepared from different parts of the guinea-pig airways. We used as antagonists BQ-123 and FR139317 (ETA receptor-selective) and PD 145065 (ETA/ETB receptor non-selective). 2. ET-1 and IRL 1620 (10(-10) M to 10(-6) M) caused similar concentration-dependent contractions of strips of guinea-pig trachea and upper bronchus. In the guinea-pig trachea without epithelium or lung parenchyma, IRL 1620 was less potent than ET-1. 3. In the trachea, contraction to ET-1 (< 10(-8) M) was preceded by a transient relaxation which was inhibited by BQ-123 (10(-5) M) or FR 139317 (10(-5) M) or by the removal of the epithelium. The concentration-response curve to ET-1 in the trachea was shifted to the right by PD 145065 (10(-5) M to 10(-4) M). PD 145065 (10(-4) M) also inhibited the response to ET-1 (3 x 10(-7) M) by 55%. Contractions induced by IRL 1620 were not affected by BQ-123 (10(-6) M) or FR139317 (10(-6) M) but were significantly attenuated by 10(-5) M of either antagonist. PD 145065 at 10(-6) M strongly attenuated and at 10(-5) M abolished contractions induced by IRL 1620.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Arai H., Hori S., Aramori I., Ohkubo H., Nakanishi S. Cloning and expression of a cDNA encoding an endothelin receptor. Nature. 1990 Dec 20;348(6303):730–732. doi: 10.1038/348730a0. [DOI] [PubMed] [Google Scholar]
  2. Aramori I., Nirei H., Shoubo M., Sogabe K., Nakamura K., Kojo H., Notsu Y., Ono T., Nakanishi S. Subtype selectivity of a novel endothelin antagonist, FR139317, for the two endothelin receptors in transfected Chinese hamster ovary cells. Mol Pharmacol. 1993 Feb;43(2):127–131. [PubMed] [Google Scholar]
  3. Barnes P. J., Cuss F. M., Palmer J. B. The effect of airway epithelium on smooth muscle contractility in bovine trachea. Br J Pharmacol. 1985 Nov;86(3):685–691. doi: 10.1111/j.1476-5381.1985.tb08946.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bigaud M., Pelton J. T. 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. doi: 10.1111/j.1476-5381.1992.tb13385.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Black P. N., Ghatei M. A., Takahashi K., Bretherton-Watt D., Krausz T., Dollery C. T., Bloom S. R. Formation of endothelin by cultured airway epithelial cells. FEBS Lett. 1989 Sep 11;255(1):129–132. doi: 10.1016/0014-5793(89)81075-0. [DOI] [PubMed] [Google Scholar]
  6. Cardell L. O., Uddman R., Edvinsson L. A novel ETA-receptor antagonist, FR 139317, inhibits endothelin-induced contractions of guinea-pig pulmonary arteries, but not trachea. Br J Pharmacol. 1993 Feb;108(2):448–452. doi: 10.1111/j.1476-5381.1993.tb12824.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Clozel M., Breu V., Burri K., Cassal J. M., Fischli W., Gray G. A., Hirth G., Löffler B. M., Müller M., Neidhart W. Pathophysiological role of endothelin revealed by the first orally active endothelin receptor antagonist. Nature. 1993 Oct 21;365(6448):759–761. doi: 10.1038/365759a0. [DOI] [PubMed] [Google Scholar]
  8. Cristol J. P., Warner T. D., Thiemermann C., Vane J. R. 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. doi: 10.1111/j.1476-5381.1993.tb12877.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. D'Orléans-Juste P., Télémaque S., Claing A., Ihara M., Yano M. Human big-endothelin-1 and endothelin-1 release prostacyclin via the activation of ET1 receptors in the rat perfused lung. Br J Pharmacol. 1992 Apr;105(4):773–775. doi: 10.1111/j.1476-5381.1992.tb09055.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Filep J. G., Battistini B., Sirois P. Pharmacological modulation of endothelin-induced contraction of guinea-pig isolated airways and thromboxane release. Br J Pharmacol. 1991 Jul;103(3):1633–1640. doi: 10.1111/j.1476-5381.1991.tb09840.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Goldie R. G., Papadimitriou J. M., Paterson J. W., Rigby P. J., Self H. M., Spina D. Influence of the epithelium on responsiveness of guinea-pig isolated trachea to contractile and relaxant agonists. Br J Pharmacol. 1986 Jan;87(1):5–14. doi: 10.1111/j.1476-5381.1986.tb10150.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Goodwin J. S. Immunomodulation by eicosanoids and anti-inflammatory drugs. Curr Opin Immunol. 1989 Dec;2(2):264–268. doi: 10.1016/0952-7915(89)90198-2. [DOI] [PubMed] [Google Scholar]
  13. Hay D. W., Farmer S. G., Raeburn D., Muccitelli R. M., Wilson K. A., Fedan J. S. Differential effects of epithelium removal on the responsiveness of guinea-pig tracheal smooth muscle to bronchoconstrictors. Br J Pharmacol. 1987 Oct;92(2):381–388. doi: 10.1111/j.1476-5381.1987.tb11334.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hay D. W. Guinea-pig tracheal epithelium and endothelin. Eur J Pharmacol. 1989 Nov 21;171(2-3):241–245. doi: 10.1016/0014-2999(89)90114-3. [DOI] [PubMed] [Google Scholar]
  15. Hay D. W., Henry P. J., Goldie R. G. Endothelin and the respiratory system. Trends Pharmacol Sci. 1993 Jan;14(1):29–32. doi: 10.1016/0165-6147(93)90111-v. [DOI] [PubMed] [Google Scholar]
  16. Hay D. W. Mechanism of endothelin-induced contraction in guinea-pig trachea: comparison with rat aorta. Br J Pharmacol. 1990 Jun;100(2):383–392. doi: 10.1111/j.1476-5381.1990.tb15814.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hay D. W. Pharmacological evidence for distinct endothelin receptors in guinea-pig bronchus and aorta. Br J Pharmacol. 1992 Aug;106(4):759–761. doi: 10.1111/j.1476-5381.1992.tb14407.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Helset E., Kjaeve J., Hauge A. Endothelin-1-induced increases in microvascular permeability in isolated, perfused rat lungs requires leukocytes and plasma. Circ Shock. 1993 Jan;39(1):15–20. [PubMed] [Google Scholar]
  19. Henry P. J. Endothelin-1 (ET-1)-induced contraction in rat isolated trachea: involvement of ETA and ETB receptors and multiple signal transduction systems. Br J Pharmacol. 1993 Sep;110(1):435–441. doi: 10.1111/j.1476-5381.1993.tb13829.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Holroyde M. C. The influence of epithelium on the responsiveness of guinea-pig isolated trachea. Br J Pharmacol. 1986 Mar;87(3):501–507. doi: 10.1111/j.1476-5381.1986.tb10192.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ihara M., Ishikawa K., Fukuroda T., Saeki T., Funabashi K., Fukami T., Suda H., Yano M. In vitro biological profile of a highly potent novel endothelin (ET) antagonist BQ-123 selective for the ETA receptor. J Cardiovasc Pharmacol. 1992;20 (Suppl 12):S11–S14. doi: 10.1097/00005344-199204002-00005. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Maggi C. A., Giuliani S., Patacchini R., Rovero P., Giachetti A., Meli A. The activity of peptides of the endothelin family in various mammalian smooth muscle preparations. Eur J Pharmacol. 1989 Dec 12;174(1):23–31. doi: 10.1016/0014-2999(89)90869-8. [DOI] [PubMed] [Google Scholar]
  24. Maggi C. A., Patacchini R., Giuliani S., Meli A. Potent contractile effect of endothelin in isolated guinea-pig airways. Eur J Pharmacol. 1989 Jan 24;160(1):179–182. doi: 10.1016/0014-2999(89)90670-5. [DOI] [PubMed] [Google Scholar]
  25. Mattoli S., Mezzetti M., Riva G., Allegra L., Fasoli A. Specific binding of endothelin on human bronchial smooth muscle cells in culture and secretion of endothelin-like material from bronchial epithelial cells. Am J Respir Cell Mol Biol. 1990 Aug;3(2):145–151. doi: 10.1165/ajrcmb/3.2.145. [DOI] [PubMed] [Google Scholar]
  26. Ninomiya H., Uchida Y., Saotome M., Nomura A., Ohse H., Matsumoto H., Hirata F., Hasegawa S. Endothelins constrict guinea pig tracheas by multiple mechanisms. J Pharmacol Exp Ther. 1992 Aug;262(2):570–576. [PubMed] [Google Scholar]
  27. Noguchi K., Noguchi Y., Hirose H., Nishikibe M., Ihara M., Ishikawa K., Yano M. Role of endothelin ETB receptors in bronchoconstrictor and vasoconstrictor responses in guinea-pigs. Eur J Pharmacol. 1993 Mar 16;233(1):47–51. doi: 10.1016/0014-2999(93)90347-k. [DOI] [PubMed] [Google Scholar]
  28. Peacock A. J., Dawes K. E., Shock A., Gray A. J., Reeves J. T., Laurent G. J. Endothelin-1 and endothelin-3 induce chemotaxis and replication of pulmonary artery fibroblasts. Am J Respir Cell Mol Biol. 1992 Nov;7(5):492–499. doi: 10.1165/ajrcmb/7.5.492. [DOI] [PubMed] [Google Scholar]
  29. Plews P. I., Abdel-Malek Z. A., Doupnik C. A., Leikauf G. D. Endothelin stimulates chloride secretion across canine tracheal epithelium. Am J Physiol. 1991 Aug;261(2 Pt 1):L188–L194. doi: 10.1152/ajplung.1991.261.2.L188. [DOI] [PubMed] [Google Scholar]
  30. Pons F., Loquet I., Touvay C., Roubert P., Chabrier P. E., Mencia-Huerta J. M., Braquet P. Comparison of the bronchopulmonary and pressor activities of endothelin isoforms ET-1, ET-2, and ET-3 and characterization of their binding sites in guinea pig lung. Am Rev Respir Dis. 1991 Feb;143(2):294–300. doi: 10.1164/ajrccm/143.2.294. [DOI] [PubMed] [Google Scholar]
  31. Sakurai T., Yanagisawa M., Takuwa Y., Miyazaki H., Kimura S., Goto K., Masaki T. Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor. Nature. 1990 Dec 20;348(6303):732–735. doi: 10.1038/348732a0. [DOI] [PubMed] [Google Scholar]
  32. Sogabe K., Nirei H., Shoubo M., Nomoto A., Ao S., Notsu Y., Ono T. Pharmacological profile of FR139317, a novel, potent endothelin ETA receptor antagonist. J Pharmacol Exp Ther. 1993 Mar;264(3):1040–1046. [PubMed] [Google Scholar]
  33. Takai M., Umemura I., Yamasaki K., Watakabe T., Fujitani Y., Oda K., Urade Y., Inui T., Yamamura T., Okada T. A potent and specific agonist, Suc-[Glu9,Ala11,15]-endothelin-1(8-21), IRL 1620, for the ETB receptor. Biochem Biophys Res Commun. 1992 Apr 30;184(2):953–959. doi: 10.1016/0006-291x(92)90683-c. [DOI] [PubMed] [Google Scholar]
  34. Tamaoki J., Kanemura T., Sakai N., Isono K., Kobayashi K., Takizawa T. Endothelin stimulates ciliary beat frequency and chloride secretion in canine cultured tracheal epithelium. Am J Respir Cell Mol Biol. 1991 May;4(5):426–431. doi: 10.1165/ajrcmb/4.5.426. [DOI] [PubMed] [Google Scholar]
  35. Turner N. C., Dollery C. T., Williams A. J. Endothelin-1-induced contractions of vascular and tracheal smooth muscle: effects of nicardipine and BRL 34915. J Cardiovasc Pharmacol. 1989;13 (Suppl 5):S180–S182. doi: 10.1097/00005344-198900135-00049. [DOI] [PubMed] [Google Scholar]
  36. Warner T. D., Allcock G. H., Corder R., Vane J. R. Use of the endothelin antagonists BQ-123 and PD 142893 to reveal three endothelin receptors mediating smooth muscle contraction and the release of EDRF. Br J Pharmacol. 1993 Oct;110(2):777–782. doi: 10.1111/j.1476-5381.1993.tb13879.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Watakabe T., Urade Y., Takai M., Umemura I., Okada T. A reversible radioligand specific for the ETB receptor: [125I]Tyr13-Suc-[Glu9,Ala11,15]-endothelin-1(8- 21), [125I]IRL 1620. Biochem Biophys Res Commun. 1992 Jun 30;185(3):867–873. doi: 10.1016/0006-291x(92)91707-w. [DOI] [PubMed] [Google Scholar]
  38. White S. R., Hathaway D. P., Umans J. G., Tallet J., Abrahams C., Leff A. R. Epithelial modulation of airway smooth muscle response to endothelin-1. Am Rev Respir Dis. 1991 Aug;144(2):373–378. doi: 10.1164/ajrccm/144.2.373. [DOI] [PubMed] [Google Scholar]
  39. 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]
  40. Wu T., Mullol J., Rieves R. D., Logun C., Hausfield J., Kaliner M. A., Shelhamer J. H. Endothelin-1 stimulates eicosanoid production in cultured human nasal mucosa. Am J Respir Cell Mol Biol. 1992 Feb;6(2):168–174. doi: 10.1165/ajrcmb/6.2.168. [DOI] [PubMed] [Google Scholar]
  41. Yanagisawa M., Kurihara H., Kimura S., Tomobe Y., Kobayashi M., Mitsui Y., Yazaki Y., Goto K., Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31;332(6163):411–415. doi: 10.1038/332411a0. [DOI] [PubMed] [Google Scholar]

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