title: Inhibitory effects of monoterpenes on human TRPA1 and the structural basis of their activity.
abstract: TRPA1, one of the transient receptor potential channels, has been reported to be involved in nociception and inflammatory pain, suggesting that this molecule could be a promising target for the development of analgesic agents. We screened several monoterpene analogs of camphor, which is known to inhibit human (h) TRPA1, to identify more effective naturally occurring TRPA1 antagonists. Borneol, 2-methylisoborneol, and fenchyl alcohol exhibited higher inhibitory effects on hTRPA1 activity than either camphor or 1,8-cineole. Our results revealed further that the S873, T874, and Y812 residues of hTRPA1 were involved in the inhibitory effects, suggesting that the hydroxyl group in the six-membered ring of the inhibitors may be interacting with these amino acids. Further research on these identified TRPA1 antagonists could lead to new pain therapeutics.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takaishi
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Uchida
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Fujita
authors.forename: Makoto
authors.initials: M
authors.lastname: Tominaga
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D015220:Calcium Channels / Q000737:chemistry / Q000187:drug effects*; D001892:Camphanes / Q000494:pharmacology; D002164:Camphor / Q000494:pharmacology; D002478:Cells, Cultured; D003511:Cyclohexanols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000077591:Eucalyptol; D057809:HEK293 Cells; D006801:Humans; D006878:Hydroxides / Q000032:analysis; D039821:Monoterpenes / Q000494:pharmacology* / Q000627:therapeutic use*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000187:drug effects*; D009636:Norbornanes; D010146:Pain / Q000188:drug therapy*; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000187:drug effects*
chemical_list: D000700:Analgesics; D015220:Calcium Channels; D001892:Camphanes; D003511:Cyclohexanols; D006878:Hydroxides; D039821:Monoterpenes; D009419:Nerve Tissue Proteins; D009636:Norbornanes; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels; C005536:2-methylisoborneol; C027328:fenchol; D002164:Camphor; C031356:hydroxide ion; C022871:isoborneol; D000077591:Eucalyptol