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:

Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor

Abstract

CORTICOTROPIN-RELEASING factor (CRF), a peptide first isolated from mammalian brain1, is critical in the regulation of the pituitary–adrenal axis, and in complementary stress-related endocrine, autonomic and behavioural responses2. Fish urotensin I and amphibian sauvagine were considered to be homologues3 of CRF until peptides even more closely related to CRF were identified in these same vertebrate classes4,5. We have characterized another mammalian member of the CRF family and have localized its urotensin-like immunoreactivity to, and cloned related complementary DNAs from, a discrete rat midbrain region. The deduced protein encodes a peptide that we name urocortin, which is related to urotensin (63% sequence identity) and CRF (45% sequence identity). Synthetic urocortin evokes secretion of adrenocortico-tropic hormone (ACTH) both in vitro and in vivo and binds and activates transfected type-1 CRF receptors6–9, the subtype expressed by pituitary corticotropes. The coincidence of urotensin-like immunoreactivity with type-2 CRF receptors10–13 in brain, and our observation that urocortin is more potent than CRF at binding and activating type-2 CRF receptors, as well as at inducing c-Fos (an index of cellular activation) in regions enriched in type-2 CRF receptors, indicate that this new peptide could be an endogenous ligand for type-2 CRF receptors.

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. Vale, W., Spiess, J., Rivier, C. & Rivier, J. Science 213, 1394–1397 (1981).

    Article  ADS  CAS  Google Scholar 

  2. Vale, W. et al. Chemical and Biological Characterization of Corticotropin Releasing Factor in Recent Progress in Hormone Research, Vol. 39, 245–270 (Academic, San Diego, 1983).

    Google Scholar 

  3. Lederis, K., Fryer, J. N., Okawara, Y., Schonrock, C. & Richter, D. in Fish Physiology (ed. Farrell, A.) 67–100 (Academic, San Diego, 1994).

    Google Scholar 

  4. Okawara, Y. et al. Proc. natn. Acad. Sci. U.S.A. 85, 8439–8443 (1988).

    Article  ADS  CAS  Google Scholar 

  5. Stenzel-Poore, M. P., Heldwein, K. A., Stenzel, P., Lee, S. & Vale, W. W. Molec. Endocr. 6, 1716–1724 (1992).

    CAS  PubMed  Google Scholar 

  6. Chen, R., Lewis, K. A., Perrin, M. H. & Vale, W. W. Proc. natn. Acad. Sci. U.S.A. 90, 8967–8971 (1993).

    Article  ADS  CAS  Google Scholar 

  7. Perrin, M. H., Donaldson, C. J., Chen, R., Lewis, K. A. & Vale, W. W. Endocrinology 133, 3058–3061 (1993).

    Article  CAS  Google Scholar 

  8. Chang, C., Pearse, R., O'Connell, S. & Rosenfeld, M. G. Neuron 11, 1187–1195 (1993).

    Article  CAS  Google Scholar 

  9. Vita, N. et al. FEBS Lett. 335, 1–5 (1993).

    Article  CAS  Google Scholar 

  10. Lovenberg, T. W. et al. Proc. natn. Acad. Sci. U.S.A. 92, 836–840 (1995).

    Article  ADS  CAS  Google Scholar 

  11. Kishimoto, T., Pearse, R. V. II, Lin, C. R. & Rosenfeld, M. G. Proc. natn. Acad: Sci. U.S.A. 92, 1108–1112 (1995).

    Article  ADS  CAS  Google Scholar 

  12. Perrin, M. et al. Proc. natn. Acad. Sci. U.S.A. 92, 2969–2973 (1995).

    Article  ADS  CAS  Google Scholar 

  13. Stenzel, P. et al. Molec. Endocr. 9, 637–645 (1995).

    CAS  PubMed  Google Scholar 

  14. Imaki, J., Imaki, T., Vale, W. & Sawchenko, P. E. Brain Res. 547, 28–36 (1991).

    Article  CAS  Google Scholar 

  15. Lovenberg, T. W., Chalmers, D. T., Liu, C. & De Souza, E. B. Endocrinology 136, 3351–3355 (1995).

    Article  Google Scholar 

  16. Potter, E. et al. Proc. natn. Acad. Sci. U.S.A. 91, 8777–8781 (1994).

    Article  ADS  CAS  Google Scholar 

  17. Ishida, I., Ichikawa, T., & Deguchi, T. Proc. natn. Acad. Sci. U.S.A. 83, 803–812 (1986).

    Article  Google Scholar 

  18. Thompson, R. C., Seasholtz, A. F. & Herbert, E. Molec. Endocr. 1, 363–370 (1987).

    Article  CAS  Google Scholar 

  19. Potter, E. et al. Proc. natn. Acad. Sci. U.S.A. 89, 4192–4196 (1992).

    Article  ADS  CAS  Google Scholar 

  20. Muglia, L. Jacobson, L., Dikkes, P. & Majzoub, J. A. Nature 373, 427–432 (1995).

    Article  ADS  CAS  Google Scholar 

  21. Loewy, A. D. in Central Regulation of Autonomic Functions (eds Loewy, A. D. & Spyer, K. M.) 268–285 (Oxford Univ. Press, New York. 1990).

    Google Scholar 

  22. Loewy, A. D., Saper, C. B. & Yamodis, N. D. Brain Res. 141, 153–159 (1978).

    Article  CAS  Google Scholar 

  23. Webster, W. R. in The Rat Nervous System (ed. Paxinos, G.) 797–831 (Academic, San Diego. 1995).

    Google Scholar 

  24. Saper, C. B., Swanson, L. W. & Cowan, W. M. J. comp. Neuro. 183, 689–706 (1979).

    Article  CAS  Google Scholar 

  25. Morgan, J. I. & Curran, T. A. Rev. Neurosci. 14, 421–451 (1991).

    Article  CAS  Google Scholar 

  26. Lederis, K. et al. Rec. Prog. Horm. Res. 41, 553–576 (1985).

    CAS  PubMed  Google Scholar 

  27. Vale, W. et al. Meth. Enzym. 103, 565–577 (1983).

    Article  CAS  Google Scholar 

  28. Sutton, S. W. et al. Endocrinology 136, 1097–1102 (1995).

    Article  CAS  Google Scholar 

  29. Chung, R. Y., Mason, P., Strassman, A., Maciewicz, R. Neurosci. Lett. 83, 13–19 (1987).

    Article  CAS  Google Scholar 

  30. Chan, R. K. W., Brown, E. R., Ericsson, A., Kovács, K. J. & Sawchenko, P. E. J. Neurosci. 13, 5125–5138 (1993).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vaughan, J., Donaldson, C., Bittencourt, J. et al. Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor. Nature 378, 287–292 (1995). https://doi.org/10.1038/378287a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/378287a0

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