title: Plumbagin, Juglone, and Boropinal as Novel TRPA1 Agonists.
abstract: A series of seven oxyprenylated phenylpropanoids and naphthoquinones were tested regarding their ability to activate transient receptor potential ankyrin subtype 1 channel (TRPA1). Three of the assayed compounds, namely, boropinal (3), juglone (5), and plumbagin (7), acted as strong modulators of TRPA1 channels with EC50 values of 9.8, 1.7, and 0.5 μM, respectively, as assessed by Ca(2+) assays. Moreover, the compounds elicited TRPA1 currents in electrophysiological whole cell recordings. We additionally provide evidence that plumbagin activated TRPA1-positive neurons isolated from mouse dorsal root ganglion neurons but did not affect sensory neurons from TRPA1-deficient mice. The high potencies of plumbagin and juglone to activate TRPA1 channels may explain the molecular basis of the mucosal irritant properties of these compounds as well as of related naphthoquinones and phytopreparations, as widely reported in the literature.
authors.affiliation: Rudolf-Boehm-Institut für Pharmakologie und Toxikologie, Universität Leipzig , Härtelstr. 16-18, 04107 Leipzig, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hill
authors.affiliation: Department of Pharmacy, University "G. D'Annunzio" of Chieti-Pescara , Via dei Vestini 31, 66100 Chieti Scalo (CH), Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Fiorito
authors.affiliation: Department of Pharmacy, University "G. D'Annunzio" of Chieti-Pescara , Via dei Vestini 31, 66100 Chieti Scalo (CH), Italy.
authors.forename: Vito Alessandro
authors.initials: VA
authors.lastname: Taddeo
authors.affiliation: Fraunhofer-Institut für Zelltherapie und Immunologie IZI, Biozentrum , Weinbergweg 22, 06120 Halle, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schulze
authors.affiliation: Rudolf-Boehm-Institut für Pharmakologie und Toxikologie, Universität Leipzig , Härtelstr. 16-18, 04107 Leipzig, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Leonhardt
authors.affiliation: Department of Pharmacy, University "G. D'Annunzio" of Chieti-Pescara , Via dei Vestini 31, 66100 Chieti Scalo (CH), Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Epifano
authors.affiliation: Department of Pharmacy, University "G. D'Annunzio" of Chieti-Pescara , Via dei Vestini 31, 66100 Chieti Scalo (CH), Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Genovese
mesh_terms: D000818:Animals; D017487:Ankyrins; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology*; D010666:Phenylpropionates / Q000737:chemistry / Q000494:pharmacology*; D011984:Sensory Receptor Cells / Q000187:drug effects; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors*
chemical_list: D017487:Ankyrins; D003374:Coumarins; D009285:Naphthoquinones; D010666:Phenylpropionates; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; C000610250:boropinal; C105832:aurapten; D002118:Calcium; C005134:juglone; C014758:plumbagin