title: Inhibition of TRPV1 channels by a naturally occurring omega-9 fatty acid reduces pain and itch.
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.
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito exterior s/n, Coyoacan 04510, Mexico.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Morales-Lázaro
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito exterior s/n, Coyoacan 04510, Mexico.
authors.forename: Itzel
authors.initials: I
authors.lastname: Llorente
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito exterior s/n, Coyoacan 04510, Mexico.
authors.forename: Félix
authors.initials: F
authors.lastname: Sierra-Ramírez
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito exterior s/n, Coyoacan 04510, Mexico.
authors.forename: Ana E
authors.initials: AE
authors.lastname: López-Romero
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito exterior s/n, Coyoacan 04510, Mexico.
authors.forename: Miguel
authors.initials: M
authors.lastname: Ortíz-Rentería
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito exterior s/n, Coyoacan 04510, Mexico.
authors.forename: Barbara
authors.initials: B
authors.lastname: Serrano-Flores
authors.affiliation: Department of Neurobiology, Duke University, 327C Bryan Research Building, Durham, North Carolina 27710, USA.
authors.forename: Sidney A
authors.initials: SA
authors.lastname: Simon
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Circuito escolar s/n, Coyoacan 04510, Mexico.
authors.forename: León D
authors.initials: LD
authors.lastname: Islas
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Circuito exterior s/n, Coyoacan 04510, Mexico.
authors.forename: Tamara
authors.initials: T
authors.lastname: Rosenbaum
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002211:Capsaicin / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D008810:Mice, Inbred C57BL; D062105:Molecular Docking Simulation; D019301:Oleic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy* / Q000473:pathology; D011537:Pruritus / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D019301:Oleic Acid; D002211:Capsaicin