Activation and Sensitization of the Capsaicin Receptor TRPV1 by Allyl Isothiocyanate

Abstract

Allyl isothiocyanate (AITC, or oil) is a powerful plant-derived irritant that functions as a defensive trait against herbivores and confers pungency to mustard and wasabi. AITC is extensively used experimentally to induce acute pain and neurogenic inflammation, which are largely mediated by the activation of nociceptive cation channels TRPA1 and TRPV1. We have recently shown that AITC activates TRPV1 through a mechanism that is similar to that underlying the activation induced by capsaicin. In the present study, we tested whether AITC sensitizes TRPV1 for activation by extracellular acidosis and heat. Patch-clamp experiments in TRPV1-expressing HEK293T cells revealed that AITC enhances the responses to low pH and heat. These results were confirmed with intracellular calcium imaging experiments in the same cells and in dorsal root ganglion (DRG) neurons isolated from Trpa1 knockout (KO) mice. The responses to low pH and heat in the presence of AITC were strongly reduced by the TRPV1 inhibitor capsazepine and nearly absent in DRG neurons isolated from Trpa1/Trpv1 KO mice. The mechanism of cross sensitization between AITC, low pH and heat seem to occur via the induction of additive shifts of the voltage dependence of channel activation. These findings indicate that TRPV1 is a locus for cross sensitization between AITC, acidosis and heat in nociceptive neurons and help understanding the molecular bases underlying the role of this channel as mediator of the algesic properties of AITC.