Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor


ENDOTHELIN-1 was initially identified as a 21-residue potent vasoconstrictor peptide produced by vascular endothelial cells, but was subsequently found to have many effects on both vascular and non-vascular tissues1,2. The discovery of three isopeptides of the endothelin family3, ET-1, ET-2 and ET-3, each possessing a diverse set of pharmacological activities of different potency, suggested the existence of several different endothelin receptor subtypes3–7. Endothelins may elicit biological responses by various signal-transduction mechanisms, including the G protein-coupled activation of phospholipase C and the activation of voltage-dependent Ca2+ channels8–10. Thus, different subtypes of the endothelin receptor may use different signal-transduction mechanisms. Here we report the cloning of a complementary DNA encoding one subtype belonging to the superf amily of G protein-coupled receptors. COS-7 cells transfected with the cDNA express specific and high-affinity binding sites for endothelins, responding to binding by the production of inositol phosphates and a transient increase in the concentration of intracellular free Ca2+. The three endothelin isopeptides are roughly equipotent in displacing 125I-labelled ET-1 binding and causing Ca2+ mobilization. A messenger RNA corresponding to the cDNA is detected in many rat tissues including the brain, kidney and lung but not in vascular smooth muscle cells. These results indicate that this cDNA encodes a 'nonselective' subtype of the receptor which is different from the vascular smooth muscle receptor.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others


  1. Yanagisawa, M. et al. Nature 332, 411–415 (1988).

    Article  ADS  CAS  Google Scholar 

  2. Yanagisawa, M. & Masaki, T. Trends pharmacol. Sci. 10, 374–378 (1989).

    Article  CAS  Google Scholar 

  3. Inoue, A. et al. proc. natn. Acad. Sci. U.S.A. 86, 2863–2867 (1989).

    Article  ADS  CAS  Google Scholar 

  4. Masuda, Y. et al. FEBS Lett. 257, 208–210 (1989).

    Article  CAS  Google Scholar 

  5. Kloog, Y., Bousso, M. D., Bdolah, A. & Sokolovski, M. FEBS Lett. 253, 199–202 (1989).

    Article  CAS  Google Scholar 

  6. Maggi, C. A. et al. Eur. J. Pharmac. 176, 1–9 (1990).

    Article  CAS  Google Scholar 

  7. Warner, T. D., de Nucci, G. & Vane, J. R. Eur. J. Pharmac. 159, 325–326 (1989).

    Article  CAS  Google Scholar 

  8. Kasuya, Y. et al. Biochem. blophys. Res. Commun. 61, 1049–1055 (1989).

    Article  Google Scholar 

  9. Takuwa, Y. et al. J. clin. Invest. 85, 653–658 (1990).

    Article  CAS  Google Scholar 

  10. Resink, T. J., Scott-Burden, T. & Buhler, F. R. Eur. J. Biochem. 189, 415–421 (1990).

    Article  CAS  Google Scholar 

  11. Seed, B. Nature 329, 840–842 (1987).

    Article  ADS  CAS  Google Scholar 

  12. Koseki, C., Imai, M., Hirata, Y., Yanagisawa, M. & Masaki, T. Am. J. Physiol. 256, R858–R866 (1989).

    Article  CAS  Google Scholar 

  13. MacCumber, M. W., Ross, C. A., Glaser, B. M. & Snyder, S. H. Proc. natn. Acad. Sci. U.S.A. 86, 7285–7289 (1989).

    Article  ADS  CAS  Google Scholar 

  14. Shaw, G. & Kamen, R. Cell 46, 659–667 (1986).

    Article  CAS  Google Scholar 

  15. von Heijine, G. Nucleic Acids Res. 14, 4683–4690 (1989).

    Article  Google Scholar 

  16. Schvartz, I., Ittoop, O. & Hazum, E. Endocrinology 126, 3218–3222 (1990).

    Article  CAS  Google Scholar 

  17. Strader, C. D., Irving, S. S. & Richard, A. F. FASEB J. 3, 1825–1832 (1989).

    Article  CAS  Google Scholar 

  18. Permentier, M. et al. Science 246, 1620–1622 (1989).

    Article  ADS  Google Scholar 

  19. McFarland, C. et al. Science 245, 494–499 (1989).

    Article  ADS  CAS  Google Scholar 

  20. Kobilka, B. et al. Science 240, 1310–1316 (1988).

    Article  ADS  CAS  Google Scholar 

  21. Fukuda, N. et al. Biochem. biophys. Res. Commun. 167, 739–745 (1990).

    Article  CAS  Google Scholar 

  22. Hirata, Y. et al. Biomed. Res. 11, 195–198 (1990).

    Article  CAS  Google Scholar 

  23. Takuwa, Y., Masaki, T. & Yamashita, K. Biochem. biophys. Res. Commun. 170, 998–1005 (1990).

    Article  CAS  Google Scholar 

  24. Bousso, M. D. et al. Biochem. biophys. Res. Commun. 162, 952–957 (1989).

    Article  Google Scholar 

  25. Ohnishi-Suzaki, A. et al. Biochem. biophys. Res. Commun. 166, 608–614 (1990).

    Article  CAS  Google Scholar 

  26. Cozza, E. N., Gomez-Sanchez, C. E., Foecking, M. F. & Chiou, S. J. clin. Invest. 84, 1032–1035 (1989).

    Article  CAS  Google Scholar 

  27. Marsault, R., Vigne, P., Breittmayer, J. P. & Frelin, C. J. J. Neurochem. 54, 2142–2144 (1990).

    Article  CAS  Google Scholar 

  28. Martin, E. R., Brenner, B. M. & Ballermann, B. J. biol. Chem. 265, 14044–14049 (1990).

    CAS  PubMed  Google Scholar 

  29. Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory, New York, 1989).

    Google Scholar 

  30. Kozak, M. Nucleic Acids Res. 12, 857–874 (1984).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Rights and permissions

Reprints and permissions

About this article

Cite this article

Sakurai, T., Yanagisawa, M., Takuwat, Y. et al. Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor. Nature 348, 732–735 (1990).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing