Trpv1 Contributes To Acrolein-Induced Toxicity.

Acrolein is a toxic and highly reactive unsaturated aldehyde, often found in cigarette smoke and vehicle exhaust gases. Likewise, acrolein derived from cyclophosphamide-treated patients constitutes the major culprit of bladder irritation during chemotherapy in cancer patient. Although, initially, its toxicity and inflammatory properties have been related to the activation of the transient receptor potential A1 (TRPA1) in nociceptive neurons, recent evidences suggests that other receptor may also play a role in acrolein-induced toxicity. Here we show that, acrolein induces chemical irritation and nocifensive response in the absence of TRPA1. Ratiometric calcium measurements and patch-clamp demonstrate that acrolein activates TRPV1 but, unlike TRPA1 that desensitizes immediately after activation, acrolein-induced activation of TRPV1 is prolonged in time. Furthermore, we identify the N-terminal amino acid residue C157 as key for acrolein-induced TRPV1 activation. Taken together, our results reveal a mechanism underlying the major role of TRPV1 as mediator for the acrolein-induced toxicity, unveiling TRPV1 as a potential therapeutic target in a wide spectrum of noxious conditions, from exposure to smoke to cancer treatment.