Article: article from journal or magazin.
Partial restoration of defective chloride conductance in DeltaF508 CF mice by trimethylamine oxide.
American Journal of Physiology. Lung Cellular and Molecular Physiology
Publication types: Journal Article
This study was designed to test the in vivo efficacy of the chemical chaperone trimethylamine oxide (TMAO) in correcting the Cl- transport defect in a mouse model of cystic fibrosis (CF). Rectal potential difference (RPD) measurements were done in matched wild-type and DeltaF508 CF mice. Mice were treated by subcutaneous injections of TMAO. Wild-type mice demonstrated a forskolin-stimulated, Cl--dependent hyperpolarization of -6.4 +/- 0.8 mV (n = 11), which was significantly increased to -13.1 +/- 1.4 mV after treatment with TMAO. DeltaF508 CF mice showed no significant responses to forskolin. Treatment with TMAO recovered a forskolin-activated RPD in DeltaF508 CF mice (-1.1 +/- 0.2 mV; n = 17) but not in CFTR null mice. The effects of TMAO were dose dependent, resulting in a slope of -0.4 +/- 0.1 mV x g(-1) x kg(-1) in DeltaF508 CF mice. The forskolin-stimulated RPD in TMAO-treated DeltaF508 CF mice was partially blocked by glibenclamide and further stimulated by apigenin. The total response to forskolin plus apigenin was -2.5 +/- 0.45 mV (n = 6 mice), corresponding to 39% of the response evoked by forskolin only in wild-type mice.
Animals, Apigenin, Chloride Channels/drug effects, Chloride Channels/physiology, Cystic Fibrosis/genetics, Cystic Fibrosis/physiopathology, Cystic Fibrosis Transmembrane Conductance Regulator/genetics, Dose-Response Relationship, Drug, Electric Conductivity, Electrophysiology, Flavonoids/pharmacology, Forskolin/pharmacology, Glyburide/pharmacology, Methylamines/pharmacology, Mice, Oxidants/pharmacology, Rectum/drug effects, Rectum/physiopathology, Reference Values
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