title: [The activation effect of nobiletin on cystic fibrosis transmembrane conductance regulator chloride channel].
abstract: Aim of the present study is to investigate activation effect of nobiletin on cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activity. CFTR-mediated iodide influx assay and patch-clamp tests were done on FRT cells stably co-transfected with human CFTR and EYFP/H148Q. Nobiletin potently activated CFTR chloride channel activity in a dose- and time-dependent manner. The CFTR blocker CFTR(inh)-172 could completely reverse the effect. Preliminary mechanism study indicated that nobiletin activated CFTR chloride channel through a direct binding way. In addition, ex vivo tests done on mice trachea showed that nobiletin time-dependently stimulated submucosal gland fluid secretion. Nobiletin may be a therapeutic lead compound in treating CFTR-related diseases including disseminated bronchiectasis.
authors.affiliation: Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, College of Life Science, Liaoning Normal University, Dalian 116033, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Yang
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.forename: Yao-Fang
authors.initials: YF
authors.lastname: Zhang
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000378:metabolism; D005088:Exocrine Glands / Q000378:metabolism*; D047309:Flavones / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D018408:Patch-Clamp Techniques; D051381:Rats; D011916:Rats, Inbred F344; D053778:Thiazolidines / Q000494:pharmacology*; D013961:Thyroid Gland / Q000166:cytology; D013997:Time Factors; D014132:Trachea / Q000378:metabolism
chemical_list: C482900:3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinone; D001565:Benzoates; C505032:CFTR protein, human; D047309:Flavones; D053778:Thiazolidines; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C008661:nobiletin