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.

An unsaturated aliphatic alcohol as a natural ligand for a mouse odorant receptor


We report the identification of a physiological receptor-volatile pair in the mouse olfactory system. By activity-guided fractionation of exocrine gland extracts and subsequent chemical analysis, (Z)-5-tetradecen-1-ol was identified as a natural ligand for a mouse odorant receptor. (Z)-5-tetradecen-1-ol is excreted into male mouse urine under androgen control and enhances urine attractiveness to female mice. This report is to our knowledge the first to describe natural product–based deorphanization of an odorant receptor.

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it


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

Figure 1: Responses of Olfr288-expressing oocytes to exocrine gland extracts.
Figure 2: Purification and identification of ligand for Olfr288 in PPG extract.
Figure 3: Z5-14:OH is a PPG-derived male urinary volatile that enhances urine attractiveness to female mice.


  1. Nei, M., Niimura, Y. & Nozawa, M. Nat. Rev. Genet. 9, 951–963 (2008).

    Article  CAS  Google Scholar 

  2. Touhara, K. & Vosshall, L.B. Annu. Rev. Physiol. 71, 307–332 (2009).

    Article  CAS  Google Scholar 

  3. Saito, H., Chi, Q., Zhuang, H., Matsunami, H. & Mainland, J.D. Sci. Signal. 2, ra9 (2009).

    Article  Google Scholar 

  4. Civelli, O. FEBS Lett. 430, 55–58 (1998).

    Article  CAS  Google Scholar 

  5. Touhara, K. Neurochem. Int. 51, 132–139 (2007).

    Article  CAS  Google Scholar 

  6. Uezono, Y. et al. Receptors Channels 1, 233–241 (1993).

    CAS  PubMed  Google Scholar 

  7. Katada, S., Nakagawa, T., Kataoka, H. & Touhara, K. Biochem. Biophys. Res. Commun. 305, 964–969 (2003).

    Article  CAS  Google Scholar 

  8. Abaffy, T., Matsunami, H. & Luetje, C.W. J. Neurochem. 97, 1506–1518 (2006).

    Article  CAS  Google Scholar 

  9. Saito, H., Kubota, M., Roberts, R.W., Chi, Q. & Matsunami, H. Cell 119, 679–691 (2004).

    Article  CAS  Google Scholar 

  10. Zhuang, H. & Matsunami, H. J. Biol. Chem. 282, 15284–15293 (2007).

    Article  CAS  Google Scholar 

  11. Von Dannecker, L.E., Mercadante, A.F. & Malnic, B. Proc. Natl. Acad. Sci. USA 103, 9310–9314 (2006).

    Article  CAS  Google Scholar 

  12. Yoshikawa, K. & Touhara, K. Chem. Senses 34, 15–23 (2009).

    Article  CAS  Google Scholar 

  13. Oka, Y. et al. Neuron 52, 857–869 (2006).

    Article  CAS  Google Scholar 

  14. Bozza, T., Feinstein, P., Zheng, C. & Mombaerts, P. J. Neurosci. 22, 3033–3043 (2002).

    Article  CAS  Google Scholar 

  15. Touhara, K. et al. Proc. Natl. Acad. Sci. USA 96, 4040–4045 (1999).

    Article  CAS  Google Scholar 

  16. Katada, S., Hirokawa, T., Oka, Y., Suwa, M. & Touhara, K. J. Neurosci. 25, 1806–1815 (2005).

    Article  CAS  Google Scholar 

  17. Tan, J., Savigner, A., Ma, M. & Luo, M. Neuron 65, 912–926 (2010).

    Article  CAS  Google Scholar 

  18. Buser, H.R., Arn, H., Guerin, P. & Rauscher, S. Anal. Chem. 55, 818–822 (1983).

    Article  CAS  Google Scholar 

  19. Bartelt, J.R., Jones, L.R. & Krick, P.T. J. Chem. Ecol. 9, 1343–1352 (1983).

    Article  CAS  Google Scholar 

  20. Evans, C.M. & Brain, F.P. Physiol. Behav. 21, 19–23 (1978).

    Article  CAS  Google Scholar 

  21. Mugford, R.A. & Nowell, N.W. Horm. Behav. 3, 39–46 (1972).

    Article  CAS  Google Scholar 

  22. Jemiolo, B., Alberts, J., Sochinski-Wiggins, S., Harvey, S. & Novotny, M. Anim. Behav. 33, 1114–1118 (1985).

    Article  Google Scholar 

  23. Lin, D.Y., Zhang, S.Z., Block, E. & Katz, L.C. Nature 434, 470–477 (2005).

    Article  CAS  Google Scholar 

  24. Horiike, M., Tanouchi, M. & Hirano, C. Agric. Biol. Chem. 44, 257–261 (1980).

    CAS  Google Scholar 

  25. Cork, A., Murlis, J. & Megenasa, T. J. Chem. Ecol. 15, 1349–1364 (1989).

    Article  CAS  Google Scholar 

  26. Krautwurst, D., Yau, K.W. & Reed, R.R. Cell 95, 917–926 (1998).

    Article  CAS  Google Scholar 

  27. Fukuda, N. et al. Eur. J. Neurosci. 27, 2665–2675 (2008).

    Article  Google Scholar 

Download references


This work was supported in part by a Grant-in-Aid for Scientific Research (S) from the Ministry of Education, Culture, Sports, Science and Technology Japan (grant 24227003), a Grant-in-Aid for Scientific Research on Priority Areas from the Japan Society for the Promotion of Science (JSPS) (grant 18077001) and a research grant from the Astellas Foundation for Research on Metabolic Disorders to K.T. K.Y. was supported by a Grant-in-Aid for JSPS fellows. We thank T. Ando for Z8-14:OH (Tokyo University of Agriculture and Technology), and T. Kikusui and T. Hattori for advice on behavioral experiments.

Author information

Authors and Affiliations



K.Y. performed experiments; H.N. identified δ-undecalactone as a synthetic ligand for Olfr288; N.M. generated the reagents; K.Y and K.T. designed the research, analyzed data and wrote the manuscript; H.W. and K.T. supervised the work.

Corresponding author

Correspondence to Kazushige Touhara.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Results (PDF 3103 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Yoshikawa, K., Nakagawa, H., Mori, N. et al. An unsaturated aliphatic alcohol as a natural ligand for a mouse odorant receptor. Nat Chem Biol 9, 160–162 (2013).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


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