Skip to main content

Thank you for visiting nature.com. 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:

A receptor subtype involved in neuropeptide-Y-induced food intake

Abstract

NEUROPEPTIDE Y (NPY) is a powerful stimulant of food intake and is proposed to activate a hypothalamic 'feeding' receptor distinct from previously cloned Y-type receptors1. This receptor was first suggested to explain a feeding response to NPY and related peptides, including NPY 2–36, that differed from their activities at the Yl receptor2. Here we report the expression cloning of a novel Y-type receptor from rat hypothalamus, which we name Y5. The complementary DNA encodes a 456-amino-acid protein with less than 35% overall identity to known Y-type receptors. The messenger RNA is found primarily in the central nervous system, including the paraventricular nucleus of the hypothalamus. The extent to which selected peptides can inhibit adenylate cyclase through the Y5 receptor and stimulate food intake in rats correspond well. Our data support the idea that the Y5 receptor is the postulated 'feeding' receptor, and may provide a new method for the study and treatment of obesity and eating disorders.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Similar content being viewed by others

References

  1. Wahlestedt, C. & Reis, D. J. A. Rev. Pharmacol. Tox. 32, 309–352 (1993).

    Article  Google Scholar 

  2. Stanley, B. G., Magdalin, W., Seirafi, A., Nguyen, M. M. & Leibowitz, S.F. Peptides 13, 581–587 (1992).

    Article  CAS  Google Scholar 

  3. Gerald, C. et al. J. biol. Chem. 270, 26758–26761 (1995).

    Article  CAS  Google Scholar 

  4. Eva, C., Keinänen, K., Monyer, H., Seeburg, P. & Sprengel, R. FEBS Lett. 271, 81–84 (1990).

    Article  CAS  Google Scholar 

  5. Larhammar, D. et al. J. biol. Chem. 267, 10935–10938 (1992).

    CAS  PubMed  Google Scholar 

  6. Herzog, H. et al. Proc. natn. Acad. Sci. U.S.A. 89, 5794–5798 (1992).

    Article  ADS  CAS  Google Scholar 

  7. Krause, J., Eva, C., Seeburg, P. H. & Sprengel, R. Molec. Pharmacol. 41, 817–821 (1992).

    CAS  Google Scholar 

  8. Eva, C., Oberto, A., Sprengel, R. & Genazzani, E. FEBS Lett. 314, 285–288 (1992).

    Article  CAS  Google Scholar 

  9. Blomqvist, A. G., Roubos, E. W., Larhammar, D. & Martens, G. J. M. Biochim. biophys. Acta 1261, 439–441 (1995).

    Article  Google Scholar 

  10. Rose, P. M. et al. J. biol. Chem. 270, 22661–22664 (1995).

    Article  CAS  Google Scholar 

  11. Rimland, J. M. et al. Molec. Pharmacol. 49, 387–390 (1996).

    CAS  Google Scholar 

  12. Schwartz, T. W. Gastroenterology 85, 1411–1425 (1983).

    CAS  PubMed  Google Scholar 

  13. Bard, J. A., Walker, M. W., Branchek, T. A. & Weinshank, R. L. J. biol. Chem. 270, 26762–26765 (1995).

    Article  CAS  Google Scholar 

  14. Lundell, I. et al. J. biol. Chem. 270, 29123–29128 (1995).

    Article  CAS  Google Scholar 

  15. Laburthe, M. et al. Endrocrinology 118, 1910–1917 (1986).

    Article  CAS  Google Scholar 

  16. Cox, H. M. & Tough, I. R. Br. J. Pharmacol. 116, 2673–2678 (1995).

    Article  CAS  Google Scholar 

  17. Ball, H. J., Shine, J. & Herzog, H. J. biol. Chem. 270, 27272–27276 (1995).

    Article  CAS  Google Scholar 

  18. Stanley, B. G. in The Biology of Neuropeptide Y and Related Peptides (eds Colmers, W. F. & Wahlestedt, C.) 457–510 (Humana, Totowa, New Jersey, 1993).

    Google Scholar 

  19. Larsen, P. J., Sheikh, S. P., Jakobsen, C. R., Schwartz, T. H. & Mikkelsen, J. D. Eur. J. Neurosci. 5, 1622–1637 (1993).

    Article  CAS  Google Scholar 

  20. Krstenansky, J. L., Owen, T. J., Buck, S. H., Hagaman, K. A. & McLean, L. R. Proc. natn. Acad. Sci. U.S.A. 86, 4377–4381 (1989).

    Article  ADS  CAS  Google Scholar 

  21. Balasubramaniam, A. et al. J. med. Chem. 37, 811–815 (1994).

    Article  CAS  Google Scholar 

  22. Rudolf, K. et al. Eur. J. Pharmacol. 271, R11–R13 (1994).

    Article  CAS  Google Scholar 

  23. Herzog, H. et al. J. biol. Chem. 268, 6703–6707 (1993).

    CAS  PubMed  Google Scholar 

  24. Gerald, C., Walker, M. W., Branchek, T. A. & Weinshank, R. L. PCT Int. Patent Application WO 95/21245 (1995).

  25. Bard, J. A., Walker, M. W., Branchek, T. A. & Weinshank, R. L. PCT Int. Patent Application WO 95/17906 (1995).

  26. Harrigan, M. Y., Campbell, N. F. & Bourgeois, S. Molec. Endocr. 5, 1331–1338 (1991).

    Article  CAS  Google Scholar 

  27. Gerald, C. et al. EMBO J. 14, 2806–2815 (1995).

    Article  CAS  Google Scholar 

  28. Durkin, M. M. et al. Molec. Brain Res. 33, 7–21 (1995).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gerald, C., Walker, M., Criscione, L. et al. A receptor subtype involved in neuropeptide-Y-induced food intake. Nature 382, 168–171 (1996). https://doi.org/10.1038/382168a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/382168a0

This article is cited by

Comments

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.

Search

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