Enhanced activation of the transient receptor potential channel TRPA1 by ajoene, an allicin derivative.
TRPA1 is a calcium-permeable, nonselective cation channel expressed in the dorsal root ganglion and trigeminal ganglia nociceptive neurons. It is activated by the pungent compounds in mustard oil (AITC, allyl isothiocyanate), cinnamon (cinnamaldehyde), garlic (allicin), and is believed to mediate the inflammatory actions of environmental irritants and proalgesic agents. Thiosulfinate (allicin) and isothiocyanate (AITC) compounds contain reactive electrophilic chemical groups that react with cysteine residues within the TRPA1 channel N terminus, leading to channel activation. Ajoene also contains reactive electrophilic chemical groups likely to target TRPA1 channel. Here, we have used voltage-clamp recordings to show that TRPA1-responses are enhanced by ajoene application in a Xenopus oocyte expression system. Though ajoene alone did not activate TRPA1, subsequent application of ajoene enhanced the AITC-, allicin- and depolarization-induced responses of TRPA1. Moreover, when increasing concentrations of ajoene were applied along with constant concentrations of allicin or AITC, stronger responses were elicited. These findings suggest that ajoene is a novel TRPA1 channel enhancer, operating in a channel-opening-dependent manner.
Yassaka
Ricardo Tsuneo
RT
Neuroscience Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), AIST Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Inagaki
Hidetoshi
H
Fujino
Tsuchiyoshi
T
Nakatani
Kei
K
Kubo
Tai
T
D000818:Animals; D001703:Biophysics; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004220:Disulfides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D016166:Free Radical Scavengers / Q000494:pharmacology; D017879:Isothiocyanates / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects* / Q000235:genetics*; D008845:Microinjections; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D033661:Oocysts; D018408:Patch-Clamp Techniques / Q000379:methods; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013441:Sulfinic Acids / Q000494:pharmacology; D013454:Sulfoxides; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus
D015220:Calcium Channels; D004220:Disulfides; D016166:Free Radical Scavengers; D017879:Isothiocyanates; D009419:Nerve Tissue Proteins; D010975:Platelet Aggregation Inhibitors; D013441:Sulfinic Acids; D013454:Sulfoxides; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels; C006452:allicin; C041942:2,3,4-tri-O-acetylarabinopyranosyl isothiocyanate; C048980:ajoene