title: Lysophosphatidic acid directly activates TRPV1 through a C-terminal binding site.
abstract: Since 1992, there has been growing evidence that the bioactive phospholipid lysophosphatidic acid (LPA), whose amounts are increased upon tissue injury, activates primary nociceptors resulting in neuropathic pain. The TRPV1 ion channel is expressed in primary afferent nociceptors and is activated by physical and chemical stimuli. Here we show that in control mice LPA produces acute pain-like behaviors, which are substantially reduced in Trpv1-null animals. Our data also demonstrate that LPA activates TRPV1 through a unique mechanism that is independent of G protein-coupled receptors, contrary to what has been widely shown for other ion channels, by directly interacting with the C terminus of the channel. We conclude that TRPV1 is a direct molecular target of the pain-producing molecule LPA and that this constitutes, to our knowledge, the first example of LPA binding directly to an ion channel to acutely regulate its function.
authors.affiliation: Departamento de Neurodesarrollo y Fisiología, División Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Distrito Federal, México.
authors.forename: Andrés
authors.initials: A
authors.lastname: Nieto-Posadas
authors.forename: Giovanni
authors.initials: G
authors.lastname: Picazo-Juárez
authors.forename: Itzel
authors.initials: I
authors.lastname: Llorente
authors.forename: Andrés
authors.initials: A
authors.lastname: Jara-Oseguera
authors.forename: Sara
authors.initials: S
authors.lastname: Morales-Lázaro
authors.forename: Diana
authors.initials: D
authors.lastname: Escalante-Alcalde
authors.forename: León D
authors.initials: LD
authors.lastname: Islas
authors.forename: Tamara
authors.initials: T
authors.lastname: Rosenbaum
mesh_terms: D000818:Animals; D001665:Binding Sites; D008246:Lysophospholipids / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010146:Pain / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism; D050916:TRPV Cation Channels / Q000172:deficiency / Q000378:metabolism*
chemical_list: D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C032881:lysophosphatidic acid
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