The capsaicin receptor TRPV1 is a crucial mediator of the noxious effects of mustard oil |
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Authors: | Everaerts Wouter Gees Maarten Alpizar Yeranddy A Farre Ricard Leten Cindy Apetrei Aurelia Dewachter Ilse van Leuven Fred Vennekens Rudi De Ridder Dirk Nilius Bernd Voets Thomas Talavera Karel |
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Affiliation: | 1 Laboratory for Ion Channel Research, Department of Molecular Cell Biology, KU Leuven, 3000 Leuven, Belgium 2 Laboratory of Experimental Urology, Department of Surgery, KU Leuven, 3000 Leuven, Belgium 3 TRPLe, TRP Research Platform Leuven, 3000 Leuven, Belgium 4 Center for Gastroenterological Research, KU Leuven, 3000 Leuven, Belgium and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Instituto de Salud Carlos III, Spain 5 Department of Physics, Laboratory of Molecular Biophysics and Medical Physics, Alexandru I. Cuza University, 700506 Iasi, Romania 6 Laboratory of Experimental Genetics and Transgenesis, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium |
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Abstract: | Mustard oil (MO) is a plant-derived irritant that has been extensively used in experimental models to induce pain and inflammation. The noxious effects of MO are currently ascribed to specific activation of the cation channel TRPA1 in nociceptive neurons. In contrast to this view, we show here that the capsaicin receptor TRPV1 has a surprisingly large contribution to aversive and pain responses and visceral irritation induced by MO. Furthermore, we found that this can be explained by previously unknown properties of this compound. First, MO has a bimodal effect on TRPA1, producing current inhibition at millimolar concentrations. Second, it directly and stably activates mouse and human recombinant TRPV1, as well as TRPV1 channels in mouse sensory neurons. Finally, physiological temperatures enhance MO-induced TRPV1 stimulation. Our results refute the dogma that TRPA1 is the sole nocisensor for MO and motivate a revision of the putative roles of these channels in models of MO-induced pain and inflammation. We propose that TRPV1 has a generalized role in the detection of irritant botanical defensive traits and in the coevolution of multiple mammalian and plant species. |
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