title: Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin.
abstract: Six members of the mammalian transient receptor potential (TRP) ion channels respond to varied temperature thresholds. The natural compounds capsaicin and menthol activate noxious heat-sensitive TRPV1 and cold-sensitive TRPM8, respectively. The burning and cooling perception of capsaicin and menthol demonstrate that these ion channels mediate thermosensation. We show that, in addition to noxious cold, pungent natural compounds present in cinnamon oil, wintergreen oil, clove oil, mustard oil, and ginger all activate TRPA1 (ANKTM1). Bradykinin, an inflammatory peptide acting through its G protein-coupled receptor, also activates TRPA1. We further show that phospholipase C is an important signaling component for TRPA1 activation. Cinnamaldehyde, the most specific TRPA1 activator, excites a subset of sensory neurons highly enriched in cold-sensitive neurons and elicits nociceptive behavior in mice. Collectively, these data demonstrate that TRPA1 activation elicits a painful sensation and provide a potential molecular model for why noxious cold can paradoxically be perceived as burning pain.
authors.affiliation: Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bandell
authors.forename: Gina M
authors.initials: GM
authors.lastname: Story
authors.forename: Sun Wook
authors.initials: SW
authors.lastname: Hwang
authors.forename: Veena
authors.initials: V
authors.lastname: Viswanath
authors.forename: Samer R
authors.initials: SR
authors.lastname: Eid
authors.forename: Matt J
authors.initials: MJ
authors.lastname: Petrus
authors.forename: Taryn J
authors.initials: TJ
authors.lastname: Earley
authors.forename: Ardem
authors.initials: A
authors.lastname: Patapoutian
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology*; D016466:CHO Cells; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003080:Cold Temperature / Q000009:adverse effects*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D007473:Ion Channels; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D000171:Acrolein; D010738:Type C Phospholipases; D001920:Bradykinin; C012843:cinnamaldehyde