Journal
NATURE COMMUNICATIONS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms13092
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Funding
- Direccion General de Asuntos del Personal Academico (DGAPA)-Programa de Apoyo a Proyectos de Investigacion e Inovacion Tecnologica (PAPIIT) [IN200314]
- Consejo Nacional de Ciencia y Tecnologia (CONACyT) [CB-2014-01-238399]
- Marcos Moshinsky foundation
- DGAPA-PAPIIT [IN209515, IA202815]
- CONACyT [248499]
- Fronteras en la Ciencia CONACyT [77]
- Beca L'Oreal-UNESCO-CONACyT-AMC
- DGTIC-UNAM [SC15-1-IR-96]
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The transient receptor potential vanilloid 1 (TRPV1) ion channel is mainly found in primary nociceptive afferents whose activity has been linked to pathophysiological conditions including pain, itch and inflammation. Consequently, it is important to identify naturally occurring antagonists of this channel. Here we show that a naturally occurring monounsaturated fatty acid, oleic acid, inhibits TRPV1 activity, and also pain and itch responses in mice by interacting with the vanilloid (capsaicin)-binding pocket and promoting the stabilization of a closed state conformation. Moreover, we report an itch-inducing molecule, cyclic phosphatidic acid, that activates TRPV1 and whose pruritic activity, as well as that of histamine, occurs through the activation of this ion channel. These findings provide insights into the molecular basis of oleic acid inhibition of TRPV1 and also into a way of reducing the pathophysiological effects resulting from its activation.
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