title: [Thermosensitive TRP channels and brain function].
abstract: Capsaicin receptor TRPV1 and wasabi receptor TRPA1 are expressed in the unmyelinated C fiber nociceptors and activated by various nociceptive stimuli causing pain in our body. Their involvement in nociception was proven with behavior studies using mice lacking TRPV1 and TRPA1. TRPV1 was found to interact with a calcium-activated chloride channel, anoctamin1 (ANO1), and calcium ions entering the primary sensory neurons activated ANO1, leading to chloride efflux which resulted in further depolarization. This is a novel pain-enhancing mechanism. A splicing variant of mouse TRPA1 (TRPA1b) was identified, and TRPA1b was found to bind to the full length TRPA1 (TRPA1a) and enhance the translocation of TRPA1a to the plasma membrane, leading to the increase in TRPA1 activity. The increase in TRPA1b transcript in the inflammatory and neuropathic pain conditions suggests the involvement of TRPA1b in the increased pain sensation under pathological conditions. Regulation of TRPV1/ANO1 complex formation or TRPA1b production could be a promising way to develop novel analgesic agents.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tominaga
mesh_terms: D000818:Animals; D000075369:Anoctamin-1; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology*; D018118:Chloride Channels / Q000502:physiology; D002712:Chlorides / Q000378:metabolism; D055808:Drug Discovery; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D009437:Neuralgia / Q000188:drug therapy / Q000235:genetics*; D059225:Nociception / Q000502:physiology*; D009619:Nociceptors / Q000378:metabolism; D011485:Protein Binding; D011984:Sensory Receptor Cells / Q000502:physiology; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000378:metabolism / Q000502:physiology*; D050051:Transient Receptor Potential Channels / Q000378:metabolism / Q000502:physiology*
chemical_list: C476213:ANO1 protein, human; D000075369:Anoctamin-1; D015220:Calcium Channels; D018118:Chloride Channels; D002712:Chlorides; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D002118:Calcium