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Inhibition of TRPV1 channels by a naturally occurring omega-9 fatty acid reduces pain and itch

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  • Sara L. Morales-Lázaro

    (Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito exterior s/n)

  • Itzel Llorente

    (Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito exterior s/n)

  • Félix Sierra-Ramírez

    (Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito exterior s/n)

  • Ana E. López-Romero

    (Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito exterior s/n)

  • Miguel Ortíz-Rentería

    (Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito exterior s/n)

  • Barbara Serrano-Flores

    (Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito exterior s/n)

  • Sidney A. Simon

    (Duke University)

  • León D. Islas

    (Facultad de Medicina, Universidad Nacional Autónoma de México, Circuito escolar s/n)

  • Tamara Rosenbaum

    (Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito exterior s/n)

Abstract

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.

Suggested Citation

  • Sara L. Morales-Lázaro & Itzel Llorente & Félix Sierra-Ramírez & Ana E. López-Romero & Miguel Ortíz-Rentería & Barbara Serrano-Flores & Sidney A. Simon & León D. Islas & Tamara Rosenbaum, 2016. "Inhibition of TRPV1 channels by a naturally occurring omega-9 fatty acid reduces pain and itch," Nature Communications, Nature, vol. 7(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13092
    DOI: 10.1038/ncomms13092
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    Cited by:

    1. Arthur Neuberger & Mai Oda & Yury A. Nikolaev & Kirill D. Nadezhdin & Elena O. Gracheva & Sviatoslav N. Bagriantsev & Alexander I. Sobolevsky, 2023. "Human TRPV1 structure and inhibition by the analgesic SB-366791," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

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