Isothiocyanates from Wasabia japonica activate transient receptor potential ankyrin 1 channel

Chem Senses. 2012 Nov;37(9):809-18. doi: 10.1093/chemse/bjs065. Epub 2012 Aug 6.


6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) and 6-(methylthio)hexyl isothiocyanate (6-MTITC) have low pungency and are responsible for the fresh flavor of wasabi (Wasabia japonica [Miq] Matsumura). In this study, we found that these two isothiocyanates activate transient receptor potential ankyrin 1 (TRPA1), and 6-MSITC activates transient receptor potential vanilloid 1 (TRPV1), but not other transient receptor potential channels expressed in sensory neurons. Both 6-MSITC and 6-MTITCinduced intracellular Ca(2+) increases in human embryonic kidney-derived 293 cells expressing mouse TRPA1 (mTRPA1) as measured by Ca(2+) imaging. In whole-cell patch-clamp recordings, 6-MSITC and 6-MTITC dose-dependently activated both mTRPA1 (EC(50) = 147±26 µM for 6-MSITC and 30±3 µM for 6-MTITC) and human TRPA1 (hTRPA1; EC(50) = 39±4 µM for 6-MSITC and 34±3 µM for 6-MTITC). In addition, TRPA1 N-terminal cysteines, which are reported to be important for channel activation by electrophilic ligands, were involved in 6-MSITC- and 6-MTITC-evoked TRPA1 activation. These isothiocyanates also activated endogenous TRPA1 expressed in mouse dorsal root ganglion neurons and intraplantar injection of 10-30 mM 6-MSITC-evoked pain-related behaviors in mice. These results indicate the following: 1) 6-MSITC and 6-MTITC activate both mTRPA1 and hTRPA1; 2) 6-MSITC activates mTRPV1; and 3) the pharmacological functions of these isothiocyanates could be derived from TRPA1 activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channels / metabolism
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / physiology
  • HEK293 Cells
  • Humans
  • Isothiocyanates / chemistry
  • Isothiocyanates / pharmacology*
  • Mice
  • Mice, Knockout
  • Mutation
  • Nerve Tissue Proteins / metabolism
  • Patch-Clamp Techniques
  • Sensory Receptor Cells / drug effects*
  • Sensory Receptor Cells / physiology
  • Sulfides / chemistry
  • Sulfides / pharmacology*
  • TRPA1 Cation Channel
  • Transient Receptor Potential Channels / deficiency
  • Transient Receptor Potential Channels / genetics
  • Transient Receptor Potential Channels / metabolism*
  • Wasabia / metabolism*


  • 6-(Methylsulfinyl)hexyl isothiocyanate
  • Calcium Channels
  • Isothiocyanates
  • Nerve Tissue Proteins
  • Sulfides
  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • Transient Receptor Potential Channels
  • Trpa1 protein, mouse
  • 6-methylthiohexyl isothiocyanate
  • Calcium