The activation effect of nobiletin on cystic fibrosis transmembrane conductance regulator chloride channel.
- Author:
Shuang YANG
1
;
Bo YU
;
Yao-Fang ZHANG
;
Xue WANG
;
Hong YANG
Author Information
1. Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, College of Life Science, Liaoning Normal University, Dalian 116033, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Benzoates;
pharmacology;
Cystic Fibrosis Transmembrane Conductance Regulator;
antagonists & inhibitors;
drug effects;
metabolism;
Dose-Response Relationship, Drug;
Epithelial Cells;
metabolism;
Exocrine Glands;
secretion;
Flavones;
administration & dosage;
pharmacology;
Humans;
Mice;
Patch-Clamp Techniques;
Rats;
Rats, Inbred F344;
Thiazolidines;
pharmacology;
Thyroid Gland;
cytology;
Time Factors;
Trachea;
secretion
- From:
Acta Pharmaceutica Sinica
2013;48(6):848-854
- CountryChina
- Language:Chinese
-
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.