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Allyl isothiocyanate sensitizes TRPV1 to heat stimulation.
Pflugers Arch. 2014 Mar; 466(3):507-15.PA

Abstract

The powerful plant-derived irritant allyl isothiocyanate (AITC, aka mustard oil) induces hyperalgesia to heat in rodents and humans through mechanisms that are not yet fully understood. It is generally believed that AITC activates the broadly tuned chemosensory cation channel transient receptor potential cation channel subfamily A member 1 (TRPA1), triggering an inflammatory response that sensitizes the heat sensor transient receptor potential cation channel subfamily V member 1 (TRPV1). In the view of recent data demonstrating that AITC can directly activate TRPV1, we here explored the possibility that this compound sensitizes TRPV1 to heat stimulation in a TRPA1-independent manner. Patch-clamp recordings and intracellular Ca(2+) imaging experiments in HEK293T cells over-expressing mouse TRPV1 revealed that the increase in channel activation induced by heating is larger in the presence of AITC than in control conditions. The analysis of the effects of AITC and heat on the current-voltage relationship of TRPV1 indicates that the mechanism of sensitization is based on additive shifts of the voltage dependence of activation towards negative voltages. Finally, intracellular Ca(2+) imaging experiments in mouse sensory neurons isolated from Trpa1 KO mice yielded that AITC enhances the response to heat, specifically in the subpopulation expressing TRPV1. Furthermore, this effect was strongly reduced by the TRPV1 inhibitor capsazepine and virtually absent in neurons isolated from double Trpa1/Trpv1 KO mice. Taken together, these findings demonstrate that TRPV1 is a locus for cross sensitization between AITC and heat in sensory neurons and may help explaining, at least in part, the role of this channel in AITC-induced hyperalgesia to heat.

Authors+Show Affiliations

Laboratory for Ion Channel Research, Department of Cellular and Molecular Medicine and TRP Research Platform Leuven (TRPLe), KU Leuven, 3000, Leuven, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23955021

Citation

Alpizar, Yeranddy A., et al. "Allyl Isothiocyanate Sensitizes TRPV1 to Heat Stimulation." Pflugers Archiv : European Journal of Physiology, vol. 466, no. 3, 2014, pp. 507-15.
Alpizar YA, Boonen B, Gees M, et al. Allyl isothiocyanate sensitizes TRPV1 to heat stimulation. Pflugers Arch. 2014;466(3):507-15.
Alpizar, Y. A., Boonen, B., Gees, M., Sanchez, A., Nilius, B., Voets, T., & Talavera, K. (2014). Allyl isothiocyanate sensitizes TRPV1 to heat stimulation. Pflugers Archiv : European Journal of Physiology, 466(3), 507-15. https://doi.org/10.1007/s00424-013-1334-9
Alpizar YA, et al. Allyl Isothiocyanate Sensitizes TRPV1 to Heat Stimulation. Pflugers Arch. 2014;466(3):507-15. PubMed PMID: 23955021.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Allyl isothiocyanate sensitizes TRPV1 to heat stimulation. AU - Alpizar,Yeranddy A, AU - Boonen,Brett, AU - Gees,Maarten, AU - Sanchez,Alicia, AU - Nilius,Bernd, AU - Voets,Thomas, AU - Talavera,Karel, Y1 - 2013/08/18/ PY - 2013/07/30/received PY - 2013/07/31/accepted PY - 2013/8/20/entrez PY - 2013/8/21/pubmed PY - 2014/10/12/medline SP - 507 EP - 15 JF - Pflugers Archiv : European journal of physiology JO - Pflugers Arch VL - 466 IS - 3 N2 - The powerful plant-derived irritant allyl isothiocyanate (AITC, aka mustard oil) induces hyperalgesia to heat in rodents and humans through mechanisms that are not yet fully understood. It is generally believed that AITC activates the broadly tuned chemosensory cation channel transient receptor potential cation channel subfamily A member 1 (TRPA1), triggering an inflammatory response that sensitizes the heat sensor transient receptor potential cation channel subfamily V member 1 (TRPV1). In the view of recent data demonstrating that AITC can directly activate TRPV1, we here explored the possibility that this compound sensitizes TRPV1 to heat stimulation in a TRPA1-independent manner. Patch-clamp recordings and intracellular Ca(2+) imaging experiments in HEK293T cells over-expressing mouse TRPV1 revealed that the increase in channel activation induced by heating is larger in the presence of AITC than in control conditions. The analysis of the effects of AITC and heat on the current-voltage relationship of TRPV1 indicates that the mechanism of sensitization is based on additive shifts of the voltage dependence of activation towards negative voltages. Finally, intracellular Ca(2+) imaging experiments in mouse sensory neurons isolated from Trpa1 KO mice yielded that AITC enhances the response to heat, specifically in the subpopulation expressing TRPV1. Furthermore, this effect was strongly reduced by the TRPV1 inhibitor capsazepine and virtually absent in neurons isolated from double Trpa1/Trpv1 KO mice. Taken together, these findings demonstrate that TRPV1 is a locus for cross sensitization between AITC and heat in sensory neurons and may help explaining, at least in part, the role of this channel in AITC-induced hyperalgesia to heat. SN - 1432-2013 UR - https://www.unboundmedicine.com/medline/citation/23955021/Allyl_isothiocyanate_sensitizes_TRPV1_to_heat_stimulation_ L2 - https://dx.doi.org/10.1007/s00424-013-1334-9 DB - PRIME DP - Unbound Medicine ER -