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 ΔF508 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. ΔF508 CF mice showed no significant responses to forskolin. Treatment with TMAO recovered a forskolin-activated RPD in ΔF508 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 ΔF508 CF mice. The forskolin-stimulated RPD in TMAO-treated ΔF508 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.
CITATION STYLE
Fischer, H., Fukuda, N., Barbry, P., Illek, B., Sartori, C., & Matthay, M. A. (2001). Partial restoration of defective chloride conductance in ΔF508 CF mice by trimethylamine oxide. American Journal of Physiology - Lung Cellular and Molecular Physiology. American Physiological Society. https://doi.org/10.1152/ajplung.2001.281.1.l52
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