2-3-4-tri-o-acetylarabinopyranosyl-isothiocyanate and ajoene

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.

Topics: Animals; Biophysics; Calcium Channels; Disulfides; Dose-Response Relationship, Drug; Drug Interactions; Electric Stimulation; Free Radical Scavengers; Isothiocyanates; Membrane Potentials; Microinjections; Models, Molecular; Nerve Tissue Proteins; Oocysts; Patch-Clamp Techniques; Platelet Aggregation Inhibitors; Sulfinic Acids; Sulfoxides; Transient Receptor Potential Channels; TRPA1 Cation Channel; Xenopus