A single N-terminal cysteine in TRPV1 determines activation by pungent compounds from onion and garlic

Nat Neurosci. 2008 Mar;11(3):255-61. doi: 10.1038/nn2056. Epub 2008 Feb 24.

Abstract

Some members of the transient receptor potential (TRP) family of cation channels mediate sensory responses to irritant substances. Although it is well known that TRPA1 channels are activated by pungent compounds found in garlic, onion, mustard and cinnamon extracts, activation of TRPV1 by these extracts remains controversial. Here we establish that TRPV1 is activated by pungent extracts from onion and garlic, as well as by allicin, the active compound in these preparations, and participates together with TRPA1 in the pain-related behavior induced by this compound. We found that in TRPV1 these agents act by covalent modification of cysteine residues. In contrast to TRPA1 channels, modification of a single cysteine located in the N-terminal region of TRPV1 was necessary and sufficient for all the effects we observed. Our findings point to a conserved mechanism of activation in TRP channels, which provides new insights into the molecular basis of noxious stimuli detection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allium / chemistry*
  • Amino Acid Sequence / physiology
  • Animals
  • Cell Line
  • Conserved Sequence
  • Cysteine / chemistry
  • Evolution, Molecular
  • Female
  • Garlic / chemistry
  • Humans
  • Male
  • Membrane Potentials / drug effects
  • Membrane Potentials / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nociceptors / drug effects
  • Nociceptors / metabolism
  • Onions / chemistry
  • Pain / chemically induced*
  • Pain / metabolism*
  • Plant Extracts / pharmacology*
  • Protein Structure, Tertiary
  • Sulfinic Acids / pharmacology
  • TRPV Cation Channels / chemistry
  • TRPV Cation Channels / drug effects*
  • TRPV Cation Channels / metabolism*

Substances

  • Plant Extracts
  • Sulfinic Acids
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • allicin
  • Cysteine