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A capsaicin-receptor homologue with a high threshold for noxious heat

Author

Listed:
  • Michael J. Caterina

    (University of California)

  • Tobias A. Rosen

    (University of California)

  • Makoto Tominaga

    (University of California)

  • Anthony J. Brake

    (University of California)

  • David Julius

    (University of California)

Abstract

Pain-producing heat is detected by several classes of nociceptive sensory neuron that differ in their thermal response thresholds1,2,3. The cloned capsaicin receptor, also known as the vanilloid receptor subtype 1 (VR1), is a heat-gated ion channel that has been proposed to mediate responses of small-diameter sensory neurons to moderate (43 °C) thermal stimuli4,5. VR1 is also activated by protons, indicating that it may participate in the detection of noxious thermal and chemical stimuli in vivo. Here we identify a structurally related receptor, VRL-1, that does not respond to capsaicin, acid or moderate heat. Instead, VRL-1 is activated by high temperatures, with a threshold of ∼52 °C. Within sensory ganglia, VRL-1 is most prominently expressed by a subset of medium- to large-diameter neurons, making it a candidate receptor for transducing high-threshold heat responses in this class of cells. VRL-1 transcripts are not restricted to the sensory nervous system, indicating that this channel may be activated by stimuli other than heat. We propose that responses to noxious heat involve these related, but distinct, ion-channel subtypes that together detect a range of stimulus intensities.

Suggested Citation

  • Michael J. Caterina & Tobias A. Rosen & Makoto Tominaga & Anthony J. Brake & David Julius, 1999. "A capsaicin-receptor homologue with a high threshold for noxious heat," Nature, Nature, vol. 398(6726), pages 436-441, April.
    • Handle: RePEc:nat:nature:v:398:y:1999:i:6726:d:10.1038_18906
    DOI: 10.1038/18906
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    Cited by:

    1. Liying Zhang & Charlotte Simonsen & Lucie Zimova & Kaituo Wang & Lavanya Moparthi & Rachelle Gaudet & Maria Ekoff & Gunnar Nilsson & Ute A. Hellmich & Viktorie Vlachova & Pontus Gourdon & Peter M. Zyg, 2022. "Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Arthur Neuberger & Mai Oda & Yury A. Nikolaev & Kirill D. Nadezhdin & Elena O. Gracheva & Sviatoslav N. Bagriantsev & Alexander I. Sobolevsky, 2023. "Human TRPV1 structure and inhibition by the analgesic SB-366791," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

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