Tear gasses CN, CR, and CS are potent activators of the human TRPA1 receptor.
The TRPA1 channel is activated by a number of pungent chemicals, such as allylisothiocyanate, present in mustard oil and thiosulfinates present in garlic. Most of the known activating compounds contain reactive, electrophilic chemical groups, reacting with cysteine residues in the active site of the TRPA1 channel. This covalent modification results in activation of the channel and has been shown to be reversible for several ligands. Commonly used tear gasses CN, CR and CS are also pungent chemicals, and in this study we show that they are extremely potent and selective activators of the human TRPA1 receptor. To our knowledge, these are the most potent TRPA1 agonists known to date. The identification of the molecular target for these tear gasses may open up possibilities to alleviate the effects of tear gasses via treatment with TRPA1 antagonists. In addition these results may contribute to the basic knowledge of the TRPA1 channel that is gaining importance as a pharmacological target.
Brône
Bert
B
Department of Neuroscience, Johnson and Johnson Pharmaceutical Research and Development, Division of Janssen Pharmaceutica N.V., Turnhoutseweg 30, B2340 Beerse, Belgium.
Peeters
Pieter J
PJ
Marrannes
Roger
R
Mercken
Marc
M
Nuydens
Ronny
R
Meert
Theo
T
Gijsen
Harrie J M
HJ
D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D003989:Dibenzoxazepines / Q000633:toxicity*; D016503:Drug Delivery Systems; D004594:Electrophysiology; D006801:Humans; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000187:drug effects* / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D013665:Tear Gases / Q000633:toxicity*; D050051:Transient Receptor Potential Channels / Q000819:agonists / Q000187:drug effects* / Q000378:metabolism; D009763:o-Chlorobenzylidenemalonitrile / Q000633:toxicity*; D002721:omega-Chloroacetophenone / Q000633:toxicity*
D015220:Calcium Channels; D003989:Dibenzoxazepines; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D013665:Tear Gases; D050051:Transient Receptor Potential Channels; D009763:o-Chlorobenzylidenemalonitrile; D002721:omega-Chloroacetophenone; C036433:dibenz(b,f)(1,4)oxazepine