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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzoates / pharmacology*
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Cystic Fibrosis Transmembrane Conductance Regulator* / antagonists & inhibitors
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Cystic Fibrosis Transmembrane Conductance Regulator* / drug effects
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Cystic Fibrosis Transmembrane Conductance Regulator* / metabolism
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Dose-Response Relationship, Drug
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Epithelial Cells / metabolism
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Exocrine Glands / metabolism*
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Flavones / administration & dosage
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Flavones / pharmacology*
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Humans
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Mice
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Patch-Clamp Techniques
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Rats
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Rats, Inbred F344
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Thiazolidines / pharmacology*
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Thyroid Gland / cytology
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Time Factors
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Trachea / metabolism
Substances
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3-((3-trifluoromethyl)phenyl)-5-((3-carboxyphenyl)methylene)-2-thioxo-4-thiazolidinone
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Benzoates
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CFTR protein, human
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Flavones
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Thiazolidines
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Cystic Fibrosis Transmembrane Conductance Regulator
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nobiletin