title: Activation of transient receptor potential ankyrin 1 by quercetin and its analogs.
abstract: The agonistic activity of quercetin and its analogs towards the transient receptor potential ankyrin 1 (TRPA1) has been experimentally investigated. The human TRPA1 was expressed in HEK293T cells using a tetracycline-inducible system. The activation of TRPA1 was evaluated by a fluo-4 fluorescence assay based on calcium sensing. The results of a structure-activity relationship study led to the selection of six flavonoids, all of which activated the TRPA1 channel in a dose-dependent manner. Notably, the activation of TRPA1 by these flavonoid aglycones was completely inhibited by the co-treatment of the HEK293T cells with the TRPA1-specific antagonist, HC-030031. Several flavonoid glycosides and metabolites were also evaluated, but did not activate the TRPA1 except for methylated quercetin. On the other hand, TRPV1 (vanilloid receptor) did not respond to any of the flavonoids evaluated in this study. Therefore, these data suggest that the flavonoids would be promising ligands for the TRPA1.
authors.affiliation: a School of Food and Nutritional Sciences , University of Shizuoka , Shizuoka , Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: a School of Food and Nutritional Sciences , University of Shizuoka , Shizuoka , Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Miyoshi
authors.affiliation: b Laboratory of Food & Nutritional Sciences, Faculty of Nutrition , Kobe Gakuin University , Kobe , Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ishii
authors.affiliation: c Department of Biotechnology, Faculty of Engineering , Toyama Prefectural University , Imizu , Japan.
authors.forename: Miyu
authors.initials: M
authors.lastname: Nishikawa
authors.affiliation: c Department of Biotechnology, Faculty of Engineering , Toyama Prefectural University , Imizu , Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ikushiro
authors.affiliation: a School of Food and Nutritional Sciences , University of Shizuoka , Shizuoka , Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000814:Aniline Compounds; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005456:Fluorescent Dyes; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D011687:Purines / Q000494:pharmacology; D011794:Quercetin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000235:genetics* / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D014966:Xanthenes
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; D000083:Acetanilides; D000814:Aniline Compounds; D015220:Calcium Channels; D005419:Flavonoids; C409648:Fluo 4; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; D011687:Purines; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D050051:Transient Receptor Potential Channels; D014966:Xanthenes; D011794:Quercetin; D002118:Calcium
keywords: TRPA1; flavonoid; metabolite; quercetin