title: 20-Hydroxyeicosatetraenoic acid (20-HETE) is a novel activator of transient receptor potential vanilloid 1 (TRPV1) channel.
abstract: TRPV1 is a member of the transient receptor potential ion channel family and is gated by capsaicin, the pungent component of chili pepper. It is expressed predominantly in small diameter peripheral nerve fibers and is activated by noxious temperatures >42 °C. 20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P-450 4A/4F-derived metabolite of the membrane phospholipid arachidonic acid. It is a powerful vasoconstrictor and has structural similarities with other TRPV1 agonists, e.g. the hydroperoxyeicosatetraenoic acid 12-HPETE, and we hypothesized that it may be an endogenous ligand for TRPV1 in sensory neurons innervating the vasculature. Here, we demonstrate that 20-HETE both activates and sensitizes mouse and human TRPV1, in a kinase-dependent manner, involving the residue Ser(502) in heterologously expressed hTRPV1, at physiologically relevant concentrations.
authors.affiliation: William Harvey Research Institute, Barts and the London Medical School, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom.
authors.forename: Hairuo
authors.initials: H
authors.lastname: Wen
authors.forename: Johan
authors.initials: J
authors.lastname: Östman
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Bubb
authors.forename: Catherine
authors.initials: C
authors.lastname: Panayiotou
authors.forename: John V
authors.initials: JV
authors.lastname: Priestley
authors.forename: Mark D
authors.initials: MD
authors.lastname: Baker
authors.forename: Amrita
authors.initials: A
authors.lastname: Ahluwalia
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry; D002211:Capsaicin / Q000378:metabolism*; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006893:Hydroxyeicosatetraenoic Acids / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D018408:Patch-Clamp Techniques; D012694:Serine / Q000737:chemistry; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C493921:TRPV1 protein, mouse; D016718:Arachidonic Acid; D012694:Serine; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D002211:Capsaicin