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Letters to Nature

Nature 418, 186-190 (11 July 2002) | doi:10.1038/nature00894; Received 21 February 2002; Accepted 29 May 2002; Published online 23 June 2002

TRPV3 is a temperature-sensitive vanilloid receptor-like protein

G. D. Smith1,2, M. J. Gunthorpe1,2, R. E. Kelsell3, P. D. Hayes3, P. Reilly1, P. Facer4, J. E. Wright1, J. C. Jerman5, J.-P. Walhin3, L. Ooi1, J. Egerton1, K. J. Charles1, D. Smart1, A. D. Randall1, P. Anand4 & J. B. Davis1

  1. Neurology-CEDD, GlaxoSmithKline, Third Avenue, Harlow CM19 5AW, UK
  2. Genetics Research, GlaxoSmithKline, Third Avenue, Harlow CM19 5AW, UK
  3. Discovery Research, GlaxoSmithKline, Third Avenue, Harlow CM19 5AW, UK
  4. Peripheral Neuropathy Unit, Imperial College, Hammersmith Hospital, Du Cane Rd, London W12 0NN, UK
  5. These authors contributed equally to this work

Correspondence to: J. B. Davis1 Correspondence and requests for materials should be addressed to J.B.D. (e-mail: Email: John_B_Davis@gsk.com). The GenBank accession number for human VRL3 is AJ487035.

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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.