Article abstract
Nature Neuroscience 11, 255 - 261 (2008)
Published online: 24 February 2008 | doi:10.1038/nn2056
A single N-terminal cysteine in TRPV1 determines activation by pungent compounds from onion and garlic
Héctor Salazar1,5, Itzel Llorente1,5, Andrés Jara-Oseguera1,2,5, Refugio García-Villegas3, Mika Munari4, Sharona E Gordon4, León D Islas2 & Tamara Rosenbaum1
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.
- Departamento de Biofísica, Instituto de Fisiología Celular, Circuito Exterior S/N, Ciudad Universitaria, Universidad Nacional Autónoma de México, México, D.F., 04510, Mexico.
- Departamento de Fisiología, Facultad de Medicina, Circuito escolar S/N, Ciudad Universitaria, Universidad Nacional Autónoma de México, México, D.F., 04510, Mexico.
- Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, México, D.F., 07360, Mexico.
- Department of Physiology and Biophysics, University of Washington, 1705 NE Pacific Street, Seattle, Washington, 98195, USA.
- These authors contributed equally to this work.
Correspondence to: Tamara Rosenbaum1 e-mail: trosenba@ifc.unam.mx
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