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TRPV3 is a temperature-sensitive vanilloid receptor-like protein



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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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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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.

Correspondence to J. B. Davis.

Supplementary information

  1. Supplementary Information: Table 1 (DOC 412 kb)

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Further reading

Figure 1: Genomic and protein structure of hVRL3.
Figure 2: Activation of hVR1 and hVRL3 by noxious heat, capsaicin or protons.
Figure 3: Localization of VRL3.
Figure 4: Association between VR1 and VRL3.


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