[Butyl-p-hydroxybenzoate stimulates cystic fibrosis transmembrane conductance regulator Cl- transport].
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.
Biotechnology and Molecular Pharmacology Center, Liaoning Normal University, Dalian 116029, China.
Hong
H
Ge
Ting-ting
TT
Hou
Juan-juan
JJ
Sun
Hong
H
Yang
D000818:Animals; D002460:Cell Line; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects*; D009154:Mutation; D010226:Parabens / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013961:Thyroid Gland / Q000166:cytology
D010226:Parabens; C093349:cystic fibrosis transmembrane conductance regulator delta F508; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D049452:Green Fluorescent Proteins; C038091:butylparaben