Butyl-p-hydroxybenzoate stimulates cystic fibrosis transmembrane conductance regulator Cl- transport.
- Author:
Hong GE
1
;
Ting-ting HOU
;
Juan-juan SUN
;
Hong YANG
Author Information
1. Biotechnology and Molecular Pharmacology Center, Liaoning Normal University, Dalian 116029, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Cell Line;
Cystic Fibrosis Transmembrane Conductance Regulator;
genetics;
metabolism;
Dose-Response Relationship, Drug;
Epithelial Cells;
metabolism;
Green Fluorescent Proteins;
genetics;
metabolism;
Ion Channel Gating;
drug effects;
Mutation;
Parabens;
administration & dosage;
pharmacology;
Rats;
Rats, Inbred F344;
Thyroid Gland;
cytology
- From:
Acta Pharmaceutica Sinica
2009;44(1):32-37
- CountryChina
- Language:Chinese
-
Abstract:
This study is to investigate the activation effect of butyl-p-hydroxybenzoate (Bpb) on cAMP-dependent cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel gating. A stably transfected Fischer rat thyroid (FRT) epithelial cell lines co-expressing human CFTR and a green fluorescent protein mutant with ultra-high halide sensitivity (EYFP) were used to measure CFTR-mediated iodide influx rates. Bpb was identified as an effective activator of wild-type CFTR chloride channel, it can correct delta F508-CFTR gating defects but not processing defect. Bpb can't potentiate G551D-CFTR channel gating. The activity was reversible and dose-dependent. The study also provided clues that Bpb activates CFTR chloride channel through a direct binding mechanism. Our study identified Bpb as a novel structure CFTR activator. Bpb may be useful for probing CFTR channel gating mechanisms and as a lead compound to develop pharmacological therapy for CFTR-related disease.
