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:

The human TAS2R16 receptor mediates bitter taste in response to β-glucopyranosides

Abstract

Bitter taste generally causes aversion, which protects humans from ingesting toxic substances. But bitter flavors also contribute to the palatability of food and beverages, thereby influencing nutritional habits in humans1. Although many studies have examined bitter taste2,3,4,5,6, the underlying receptor mechanisms remain poorly understood. Anatomical, functional and genetic data from rodents suggest the existence of a family of receptors that are responsive to bitter compounds7,8,9. Here we report that a human member of this family, TAS2R16, is present in taste receptor cells on the tongue and is activated by bitter β-glucopyranosides. Responses to these phytonutrients show a similar concentration dependence and desensitization in transfected cells and in experiments assessing taste perception in humans. Bitter compounds consisting of a hydrophobic residue attached to glucose by a β-glycosidic bond activate TAS2R16. Thus, TAS2R16 links the recognition of a specific chemical structure to the perception of bitter taste. If the ability of TAS2R16 to detect substances with common molecular properties is typical of the bitter receptor family, it may explain how a few receptors permit the perception of numerous bitter substances.

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

Access options

Buy this article

Purchase on Springer Link

Instant access to full article PDF

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

Figure 1: Dendrogram of the sequence relationship between members of the TAS2R gene family.
Figure 2: Membrane localization, functional expression and specificity of bitter-responsive receptors in HEK293/15 cells.
Figure 3: Functional characterization of the TAS2R16 bitter receptor by FLIPR experiments.
Figure 4: 4 Cross-densensitization and cross-adaptation of cellular and psychophysical responses elicited by β-glucopyranosides.
Figure 5: Detection of TAS2R16 mRNA by RT–PCR and in situ hybridization in human tissues.

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  1. Drewnowski, A. The science and complexity of bitter taste. Nutr. Rev. 59, 163–169 (2001).

    Article  CAS  Google Scholar 

  2. Caicedo, A. & Roper, S.D. Taste receptor cells that discriminate between bitter stimuli. Science 291, 1557–1560 (2001).

    Article  CAS  Google Scholar 

  3. Dulac, C. The physiology of taste, vintage 2000. Cell 100, 607–610 (2000).

    Article  CAS  Google Scholar 

  4. Kinnamon, S.C. A plethora of taste receptors. Neuron 25, 507–510 (2000).

    Article  CAS  Google Scholar 

  5. Lindemann, B. Receptors and transduction in taste. Nature 413, 219–225 (2001).

    Article  CAS  Google Scholar 

  6. Margolskee, R.F. Molecular mechanisms of bitter and sweet taste transduction. J. Biol. Chem. 277, 1–4 (2001).

    Article  Google Scholar 

  7. Chandrashekar, J. et al. T2Rs function as bitter taste receptors. Cell 100, 703–711 (2000).

    Article  CAS  Google Scholar 

  8. Matsunami, H., Montmayeur, J.P. & Buck, L.B. A family of candidate taste receptors in human and mouse. Nature 404, 601–604 (2000).

    Article  CAS  Google Scholar 

  9. Adler, E. et al. A novel family of mammalian taste receptors. Cell 100, 693–702 (2000).

    Article  CAS  Google Scholar 

  10. Krautwurst, D., Yau, K.W. & Reed, R.R. Identification of ligands for olfactory receptors by functional expression of a receptor library. Cell 95, 917–926 (1998).

    Article  CAS  Google Scholar 

  11. Wetzel, C.H. et al. Specificity and sensitivity of a human olfactory receptor functionally expressed in human embryonic kidney 293 cells and Xenopus laevis oocytes. J. Neurosci. 19, 7426–7433 (1999).

    Article  CAS  Google Scholar 

  12. Offermanns, S. & Simon, M.I. Gα15 and Gα16 couple a wide variety of receptors to phospholipase C. J. Biol. Chem. 270, 15175–15180 (1995).

    Article  CAS  Google Scholar 

  13. Bockaert, J. & Pin, J.P. Molecular tinkering of G protein-coupled receptors: an evolutionary success. EMBO J. 18, 1723–1729 (1999).

    Article  CAS  Google Scholar 

  14. Vane, J.R. The fight against rheumatism: from willow bark to COX-1 sparing drugs. J. Physiol. Pharmacol. 51, 573–586 (2000).

    CAS  PubMed  Google Scholar 

  15. Torre, V., Ashmore, J.F., Lamb, T.D. & Menini, A. Transduction and adaptation in sensory receptor cells. J. Neurosci. 15, 7757–7768 (1995).

    Article  CAS  Google Scholar 

  16. Ferguson, S.S. & Caron, M.G. G protein-coupled receptor adaptation mechanisms. Semin. Cell Dev. Biol. 9, 119–127 (1998).

    Article  CAS  Google Scholar 

  17. Keast, R.S. & Breslin, P.A. Cross-adaptation and bitterness inhibition of l-tryptophan, l-phenylalanine and urea: further support for shared peripheral physiology. Chem. Senses 27, 123–131 (2002).

    Article  Google Scholar 

  18. von Liebig, J. Chemische Briefe (C.F. Winter'sche Verlagshandlung, Leipzig and Heidelberg, 1844).

    Google Scholar 

  19. Kubo, I. Structural basis for bitterness based on Rabdosia diterpenes. Physiol. Behav. 56, 1203–1207 (1994).

    Article  CAS  Google Scholar 

  20. Drewnowski, A. & Gomez-Carneros, C. Bitter taste, phytonutrients, and the consumer: a review. Am. J. Clin. Nutr. 72, 1424–1435 (2000).

    Article  CAS  Google Scholar 

  21. Meyerhof, W., Wulfsen, I., Schonrock, C., Fehr, S. & Richter, D. Molecular cloning of a somatostatin-28 receptor and comparison of its expression pattern with that of a somatostatin-14 receptor in rat brain. Proc. Natl Acad. Sci. USA 89, 10267–10271 (1992).

    Article  CAS  Google Scholar 

  22. Ammon, C., Schäfer, J., Kreuzer, O.J. & Meyerhof, W. Presence of a plasma membrane targeting sequence in the amino-terminal region of the rat somatostatin receptor 3. Arch. Physiol. Biochem. 110, 137–145 (2001).

    Article  Google Scholar 

  23. Roosterman, D., Roth, A., Kreienkamp, H.J., Richter, D. & Meyerhof, W. Distinct agonist-mediated endocytosis of cloned rat somatostatin receptor subtypes expressed in insulinoma cells. J. Neuroendocrinol. 9, 741–751 (1997).

    Article  CAS  Google Scholar 

  24. Stevens, D.R. et al. Hyperpolarization-activated channels HCN1 and HCN4 mediate responses to sour stimuli. Nature 413, 631–635 (2001).

    Article  CAS  Google Scholar 

  25. Frank, O., Ottinger, H. & Hofmann, T. Characterization of an intense bitter-tasting 1H,4H-quinolizinium-7-olate by application of the taste dilution analysis, a novel bioassay for the screening and identification of taste-active compounds in foods. J. Agric. Food Chem. 49, 231–238 (2001).

    Article  CAS  Google Scholar 

  26. Mailgaard, M., Civille, G.V. & Carr, B.T. in Sensory Evaluation Techniques (eds Mailgaard, M., Civille, G.V. & Carr, B.T.) 122–159 (CRC, New York, 1999).

    Book  Google Scholar 

Download references

Acknowledgements

We thank E. Schöley-Pohl and J. Stein for technical assistance, and C.A. Barth and H. Schulz for support. We thank the Deutsche Forschungsgemeinschaft for a grant.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wolfgang Meyerhof.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bufe, B., Hofmann, T., Krautwurst, D. et al. The human TAS2R16 receptor mediates bitter taste in response to β-glucopyranosides. Nat Genet 32, 397–401 (2002). https://doi.org/10.1038/ng1014

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng1014

This article is cited by

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