Journal club 16.10.14.

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

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

Sara L. Morales-La ́zaro1, Itzel Llorente1, Fe ́lix Sierra-Ram ́ırez1, Ana E. Lo ́pez-Romero1, Miguel Ort ́ız-Renter ́ıa1, Barbara Serrano-Flores1, Sidney A. Simon2, Leo ́n D. Islas3 & Tamara Rosenbaum1

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 mono- unsaturated 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.

1 Instituto de Fisiolog ́ıa Celular, Universidad Nacional Auto ́noma de Me ́xico, Circuito exterior s/n, Coyoacan 04510, Mexico. 2 Department of Neurobiology, Duke University, 327C Bryan Research Building, Durham, North Carolina 27710, USA. 3 Departamento de Fisiolog ́ıa, Facultad de Medicina, Universidad Nacional Auto ́noma de Me ́xico, Circuito escolar s/n, Coyoacan 04510, Mexico. Correspondence and requests for materials should be addressed to T.R. (email: trosenba@ifc.unam.mx).