TRPV3 is a temperature-sensitive vanilloid receptor-like protein (original) (raw)

Nature volume 418, pages 186–190 (2002)Cite this article

Abstract

Vanilloid receptor-1 (VR1, also known as TRPV1) is a thermosensitive, nonselective cation channel that is expressed by capsaicin-sensitive sensory afferents and is activated by noxious heat, acidic pH and the alkaloid irritant capsaicin1. Although VR1 gene disruption results in a loss of capsaicin responses, it has minimal effects on thermal nociception2,3. This and other experiments—such as those showing the existence of capsaicin-insensitive heat sensors in sensory neurons4—suggest the existence of thermosensitive receptors distinct from VR1. Here we identify a member of the vanilloid receptor/TRP gene family, vanilloid receptor-like protein 3 (VRL3, also known as TRPV3), which is heat-sensitive but capsaicin-insensitive. VRL3 is coded for by a 2,370-base-pair open reading frame, transcribed from a gene adjacent to VR1, and is structurally homologous to VR1. VRL3 responds to noxious heat with a threshold of about 39 °C and is co-expressed in dorsal root ganglion neurons with VR1. Furthermore, when heterologously expressed, VRL3 is able to associate with VR1 and may modulate its responses. Hence, not only is VRL3 a thermosensitive ion channel but it may represent an additional vanilloid receptor subunit involved in the formation of heteromeric vanilloid receptor channels.

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Acknowledgements

The authors acknowledge R. Birch and R. Ravid for supply of human adult tissues; I. Gloger, C. Benham, M. Duckworth and C. Bountra for advice and encouragement; and C. Farrant for help with artwork.

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Author notes

  1. G. D. Smith, M. J. Gunthorpe and J. C. Jerman: These authors contributed equally to this work

Authors and Affiliations

  1. Neurology-CEDD, GlaxoSmithKline, Third Avenue, Harlow, CM19 5AW, UK
    G. D. Smith, M. J. Gunthorpe, P. Reilly, J. E. Wright, L. Ooi, J. Egerton, K. J. Charles, D. Smart, A. D. Randall & J. B. Davis
  2. Genetics Research, GlaxoSmithKline, Third Avenue, Harlow, CM19 5AW, UK
    R. E. Kelsell, P. D. Hayes & J.-P. Walhin
  3. Discovery Research, GlaxoSmithKline, Third Avenue, Harlow, CM19 5AW, UK
    J. C. Jerman
  4. Peripheral Neuropathy Unit, Imperial College, Hammersmith Hospital, Du Cane Rd, W12 0NN, London, UK
    P. Facer & P. Anand

Authors

  1. G. D. Smith
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  2. M. J. Gunthorpe
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  3. R. E. Kelsell
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  4. P. D. Hayes
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  5. P. Reilly
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  6. P. Facer
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  7. J. E. Wright
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  8. J. C. Jerman
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  9. J.-P. Walhin
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  10. L. Ooi
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  11. J. Egerton
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  12. K. J. Charles
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  13. D. Smart
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  14. A. D. Randall
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  15. P. Anand
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  16. J. B. Davis
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Corresponding author

Correspondence toJ. B. Davis.

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Competing interests

G.D.S., M.J.G., R.E.K., P.D.H., P.R., J.E.W., J.C.J., J.-P.W., L.O., J.E., K.J.C., D.S., A.D.R. and J.B.D. are employees of GlaxoSmithKline.

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Smith, G., Gunthorpe, M., Kelsell, R. et al. TRPV3 is a temperature-sensitive vanilloid receptor-like protein.Nature 418, 186–190 (2002). https://doi.org/10.1038/nature00894

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