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- W1992356695 abstract "In isolated hepatocytes the influence of cellular glutathione (GSH) on initial influx, net uptake and efflux of methotrexate (MTX) was determined. Endogenous glutathione in rat liver cells was depleted by either fasting of rats or by in vivo administration of phorone prior to cell preparation. The initial rate of influx of MTX was found to be higher in hepatocytes of fasted and phorone-treated rats than in those of untreated, fed control rats. The Km values for the methotrexate influx in GSH-deficient hepatocytes were up to 3 times lower than in normal cells, whereas Vmax remained unchanged. These results disclose an increased efficiency of the MTX transport system in cells with diminished cellular GSH levels. On the other hand, titration of external membrane SH groups by 203Hg p-CMBS revealed up to three times higher amounts of free SH groups on cells from starved and phorone-treated rats than on hepatocytes of fed rats. Increased efficiency of the MTX transport system in GSH-deficient cells may, therefore, be interpreted as increased capacity of the MTX transport carrier for which free membrane SH groups are known to be essential. Despite activation of initial transport of MTX here, later net accumulation of MTX became smaller than in cells with normal GSH levels. Efflux of MTX from liver cells was not influenced by fasting or phorone treatment of rats, however, the nonexchangeable pool of MTX was found to be decreased, which indicates inhibition of formation of MTX polyglutamates here. This inhibition was most likely responsible for the decreased amounts of MTX finally accumulated in GSH-deficient hepatocytes." @default.
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- W1992356695 title "Effect of depletion of cellular glutathione on methotrexate influx, efflux and retention in hepatocytes" @default.
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- W1992356695 doi "https://doi.org/10.1016/0006-2952(85)90626-4" @default.
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