Abstract
We have compared the sensitivities of normal and cystic fibrosis (CF) skin fibroblasts to the cytotoxic effects of ouabain (OB), a cardiac glycoside known to inhibit the transport of ions across cell membranes. Cells from 9 unrelated CF patients when plated at low density for 24 hours in K+ deficient medium and then exposed for 24 hours to OB at concentrations from 1 × 10−10 to 1 × 10−6M, show an increased survival when compared to normal cells. In agreement with these observations, studies of 3H-OB binding show that CF cells bind less OB than normal cells in medium lacking K+. At low drug concentrations (2-20 × 10−9M), the first order rate constant for 3H-OB binding in CF cells was approximately 70% of normal. Equilibrium binding experiments were performed in 3 sets of fibroblast strains from age-matched normal and CF individuals. In a Scatchard analysis the CF strains had 84 ± 2%, 56 ± 1%, and 88 ± 2% (mean ± S.E.M) of normal 3H-OB binding sites per mg cell protein (for each strain the difference from normal is p < .001). Previous studies by others of OB resistant mammalian cells isolated in culture showed decreased OB binding as well as a decreased ability of OB to inhibit ion transport. We have studied ion flux in normal and CF cells using 86Rb, a potassium analogue, and have shown identical inhibition of ion transport by OB in both cell types. Thus CF cells appear different from other previously described OB resistant cells. The relationship of these observations to the primary genetic defect in CF is not yet clear.
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Breslow, J., Epstein, J. & Gerald, P. DECREASED OUABAIN BINDING IN CYSTIC FIBROSIS FIBROBLASTS. Pediatr Res 11, 453 (1977). https://doi.org/10.1203/00006450-197704000-00499
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DOI: https://doi.org/10.1203/00006450-197704000-00499