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Title: Mechanisms of TRPV1 Activation and Sensitization by Allyl Isothiocyanate
Authors: Gees, Maarten ×
Aguiar Alpizar, Yeranddy
Boonen, Brett
Sanchez Linde, Alicia
Everaerts, Wouter
Segal Stanciu, Andrei
Xue, Fenquin
Janssens, Annelies
Owsianik, Grzegorz
Nilius, Bernd
Voets, Thomas
Talavera PĂ©rez, Karel #
Issue Date: Sep-2013
Publisher: American Society for Pharmacology and Experimental Therapeutics
Series Title: Molecular Pharmacology vol:84 issue:3 pages:325-334
Abstract: Allyl isothiocyanate (AITC, aka mustard oil) is a powerful irritant produced by Brassica plants as a defensive trait against herbivores and confers pungency to mustard and wasabi. AITC is widely used experimentally as inducer of acute pain and neurogenic inflammation, which are largely mediated by the activation of nociceptive cation channels TRPA1 and TRPV1. Although it is generally accepted that electrophilic agents activate these channels through covalent modification of cytosolic cysteine residues, the mechanism underlying TRPV1 activation by AITC remains unknown. Here we show that, surprisingly, AITC-induced activation of TRPV1 does not require interaction with cysteine residues, but is largely dependent on S513, a residue that is involved in capsaicin binding. Furthermore, AITC acts in a membrane-delimited manner and induces a shift of the voltage dependence of activation towards negative voltages, which is reminiscent of capsaicin effects. These data indicate that AITC acts through reversible interactions with the capsaicin binding site. Additionally, we show that TRPV1 is a locus for cross sensitization between AITC and acidosis in nociceptive neurons. Furthermore, we show that residue F660, which is known to determine the stimulation by low pH in human TRPV1, is also essential for the cross sensitization of the effects of AITC and low pH. Taken together, these findings demonstrate that not all reactive electrophiles stimulate TRPV1 via cysteine modification and help understanding the molecular bases underlying the surprisingly large role of this channel as mediator of the algesic properties of AITC.
URI: 
ISSN: 0026-895X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Cellular and Molecular Medicine - miscellaneous
Laboratory of Ion Channel Research
× corresponding author
# (joint) last author

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