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The capsaicin receptor: a heat-activated ion channel in the pain pathway

Naturevolume 389, pages816–824 (1997)Cite this article

Abstract

Capsaicin, the main pungent ingredient in ‘hot’ chilli peppers, elicits a sensation of burning pain by selectively activating sensory neurons that convey information about noxious stimuli to the central nervous system. We have used an expression cloning strategy based on calcium influx to isolate a functional cDNA encoding a capsaicin receptor from sensory neurons. This receptor is a non-selective cation channel that is structurally related to members of the TRP family of ion channels. The cloned capsaicin receptor is also activated by increases in temperature in the noxious range, suggesting that it functions as a transducer of painful thermal stimuliin vivo.

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Figure 1: Expression cloning of a capsaicin receptor using calcium imaging.
Figure 2: VR1 responds to purified vanilloids and pepper extracts.
Figure 3: VR1 responds to purified vanilloids and pepper extracts.
Figure 4: VR1 is a calcium-permeable, non-selective cation channel.
Figure 5: Capsaicin induces death of cells expressing the vanilloid receptor.
Figure 6: VR1 resembles store-operated channels.
Figure 7: VR1 resembles store-operated channels.
Figure 8: VR1 resembles store-operated channels.
Figure 9: Vanilloid receptor expression is restricted to sensory neurons.
Figure 10: Vanilloid receptor expression is restricted to sensory neurons.
Figure 11: VR1 is activated by noxious thermal stimuli.
Figure 12: VR1 is activated by noxious thermal stimuli.
Figure 13: Hydrogen ions potentiate the effect of capsaicin on VR1.

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Acknowledgements

We thank H. Kong, M. Chao and A. Brake for the dorsal root ganglian cDNA and plasmid DNA used in library construction; T. Livelli for HEK293 cells and advice regarding transfection; J.Trafton for guidance with calcium imaging proceudres; N. Guy for tissue sections; J. Poblete for technical assistance; A. Basbaum and M. Dallman for comments on the manuscript; and A. Brake and H.Ingraham for advice and encouragement. M.J.C. is a recipient of an American Cancer Society postdoctoral fellowship and a NARSAD young investigator award. This work was supported by grants from the NIH.

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Author notes

  1. Mark A. Schumacher, Makoto Tominaga and Jon D. Levine: These authors contributed equally to this study.

Authors and Affiliations

  1. Departments of Cellular and Molecular Pharmacology, San Francisco, 94143-0450, California, USA

    Michael J. Caterina, Makoto Tominaga, Tobias A. Rosen & David Julius

  2. Departments of Anesthesia, San Francisco, 94143-0450, California, USA

    Mark A. Schumacher

  3. Departments of Medicine, University of California, San Francisco, 94143-0450, California, USA

    Jon D. Levine

Authors
  1. Michael J. Caterina

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Correspondence toDavid Julius.

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Caterina, M., Schumacher, M., Tominaga, M.et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway.Nature389, 816–824 (1997). https://doi.org/10.1038/39807

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