title: TRPA1.
abstract: The transient receptor potential ankyrin subtype 1 protein (TRPA1) is a nonselective cation channel permeable to Ca(2+), Na(+), and K(+). TRPA1 is a promiscuous chemical nocisensor that is also involved in noxious cold and mechanical sensation. It is present in a subpopulation of Aδ- and C-fiber nociceptive sensory neurons as well as in other sensory cells including epithelial cells. In primary sensory neurons, Ca(2+) and Na(+) flowing through TRPA1 into the cell cause membrane depolarization, action potential discharge, and neurotransmitter release both at peripheral and central neural projections. In addition to being activated by cysteine and lysine reactive electrophiles and oxidants, TRPA1 is indirectly activated by pro-inflammatory agents via the phospholipase C signaling pathway, in which cytosolic Ca(2+) is an important regulator of channel gating. The finding that non-electrophilic compounds, including menthol and cannabinoids, activate TRPA1 may provide templates for the design of non-tissue damaging activators to fine-tune the activity of TRPA1 and raises the possibility that endogenous ligands sharing binding sites with such non-electrophiles exist and regulate TRPA1 channel activity. TRPA1 is promising as a drug target for novel treatments of pain, itch, and sensory hyperreactivity in visceral organs including the airways, bladder, and gastrointestinal tract.
authors.affiliation: Clinical and Experimental Pharmacology, Clinical Chemistry, Department of Laboratory Medicine, Lund University, Skåne University Hospital, SE-221 85, Lund, Sweden, peter.zygmunt@med.lu.se.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Zygmunt
authors.forename: Edward D
authors.initials: ED
authors.lastname: Högestätt
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002463:Cell Membrane Permeability; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D015640:Ion Channel Gating; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011487:Protein Conformation; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse