Tear gasses CN, CR, and CS are potent activators of the human TRPA1 receptor

• Published in: Toxicology and applied pharmacology Vol. 231; no. 2; pp. 150 - 156
• Main Authors: Brône, Bert, Peeters, Pieter J., Marrannes, Roger, Mercken, Marc, Nuydens, Ronny, Meert, Theo, Gijsen, Harrie J.M.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01-09-2008; Elsevier
• Subjects: 60 APPLIED LIFE SCIENCES; Agonist; Allium sativum; Biological and medical sciences; Blepharospasm; BRASSICA; Calcium Channels - drug effects; Calcium Channels - metabolism; CARBON NITRIDES; Cells, Cultured; Chemical and industrial products toxicology. Toxic occupational diseases; CYANIDES; CYSTEINE; Dibenzoxazepines - toxicity; DMSO; Drug Delivery Systems; Electrophysiology; GARLIC; GAS CHROMATOGRAPHY; Gas, fumes; HAMSTERS; Humans; Ion-channel; LIGANDS; LIQUID COLUMN CHROMATOGRAPHY; MASS SPECTROSCOPY; Medical sciences; Nerve Tissue Proteins - agonists; Nerve Tissue Proteins - drug effects; Nerve Tissue Proteins - metabolism; o-Chlorobenzylidenemalonitrile - toxicity; omega-Chloroacetophenone - toxicity; OVARIES; Patch clamp; RECEPTORS; Tear gas; Tear Gases - toxicity; Toxicology; Transient Receptor Potential Channels - agonists; Transient Receptor Potential Channels - drug effects; Transient Receptor Potential Channels - metabolism; TRPA1; TRPA1 Cation Channel; Agonist; GCMS; TRPA1; DMSO; EBA; Patch clamp; AITC; BITC; Ion-channel; CHO; CN; THC; CR; Tear gas; CS; TRP; CA (BBC); HNE; LCMS; Blepharospasm; Human; Target; TRPA1;Agonist;Ion-channel;Patch clamp;Tear gas;Blepharospasm; Activator; Toxicity; Transient receptor potential canonical protein; Mechanism of action; Biological receptor
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2008.04.005

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.