Partial restoration of defective chloride conductance in ΔF508 CF mice by trimethylamine oxide
Partial restoration of defective chloride conductance in ΔF508 CF mice by trimethylamine oxide
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DOI：
10.1152/ajplung.2001.281.1.l52
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发表时间：
2001-07-01
影响因子：
4.9
通讯作者：
Matthay, MA
中科院分区：
文献类型：
--
作者：
Fischer, H;Fukuda, N;Matthay, MA
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 Delta F508 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. Delta F508 CF mice showed no significant responses to forskolin. Treatment with TMAO recovered a forskolin-activated RPD in Delta F508 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 . g(-1) . kg(-1) in Delta F508 CF mice. The forskolin-stimulated RPD in TMAO-treated Delta F508 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.
