Abstract
Some members of the transient receptor potential (TRP) family of cation channels mediate sensory responses to irritant substances. Although it is well known that TRPA1 channels are activated by pungent compounds found in garlic, onion, mustard and cinnamon extracts, activation of TRPV1 by these extracts remains controversial. Here we establish that TRPV1 is activated by pungent extracts from onion and garlic, as well as by allicin, the active compound in these preparations, and participates together with TRPA1 in the pain-related behavior induced by this compound. We found that in TRPV1 these agents act by covalent modification of cysteine residues. In contrast to TRPA1 channels, modification of a single cysteine located in the N-terminal region of TRPV1 was necessary and sufficient for all the effects we observed. Our findings point to a conserved mechanism of activation in TRP channels, which provides new insights into the molecular basis of noxious stimuli detection.
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Acknowledgements
We thank D. Julius for providing the TRPV1 cDNA and S. Simon and M. Rosenbaum for thoughtful discussion of this manuscript. We also thank L. Ongay, A. Aguilera Jiménez, J. Barbosa, F. Sierra, C. Rivera and H. Malagón for expert technical support and R. Argüello García for his most kind gift of allicin. This work was supported by grants from Dirección General de Asuntos del Personal Académico-Universidad Nacional Autónoma de México (DGAPA-UNAM) IN201705 and IN200308 to T.R. and IN202006–39 to L.D.I. and Consejo Nacional de Ciencia y Tecnología (CONACyT) No. 58038 to T.R., No. 48990/24777 to L.D.I., and No. 43128 to R.G.-V.; and by a grant from the National Eye Institute to S.E.G.
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H.S., I.L. and A.J.O. contributed equally to this work. I.L. and T.R. carried out all site-directed mutagenesis experiments. H.S., I.L., A.J.O. and L.D.I. performed electrophysiological recordings. R.G.V. and T.R. carried out DRG neuron and behavioral experiments. L.D.I. and T.R. analyzed the data and wrote the manuscript. S.E.G. and M.M. discussed the results and commented on the manuscript.
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Salazar, H., Llorente, I., Jara-Oseguera, A. et al. A single N-terminal cysteine in TRPV1 determines activation by pungent compounds from onion and garlic. Nat Neurosci 11, 255–261 (2008). https://doi.org/10.1038/nn2056
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DOI: https://doi.org/10.1038/nn2056
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