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• W2073625052 abstract "The antioestrogens, tamoxifen and its more recent homologue toremifene, are used in the therapy of breast cancer. Tamoxifen has been reported to cause retinal changes as side effects. Both compounds inhibited glutamate uptake in retinal pigment epithelial cells, and the present study was conducted to clarify the mechanism of this inhibition. Retinal pigment epithelial cells are part of the blood-retina barrier, and their glutamate transporters are essential for retinal glutamate homeostasis. Glutamate uptake was investigated in human retinal pigment epithelial cell line D407 and in cultured pig retinal pigment epithelial cells using L-[3H]glutamate as a tracer. The cells were exposed to 7.5 microM tamoxifen and toremifene. beta-Hydroxyaspartate, a transportable inhibitor of glutamate transport, was used as a reference compound. In kinetic analyses, beta-hydroxyaspartate increased the Km constant for glutamate transport. Tamoxifen and toremifene exhibited the same effect, which indicates that inhibition evoked by them is also competitive in nature. Both drugs were more effective in the human retinal pigment epithelial cell line than in the pig retinal pigment epithelial cells. The results show for the first time that the antioestrogens tamoxifen and toremifene could possibly hamper glutamate transport by replacing glutamate as the substrate." @default.
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• W2073625052 date "2003-10-01" @default.
• W2073625052 modified "2023-10-12" @default.
• W2073625052 title "Kinetics of Inhibition of Glutamate Uptake by Antioestrogens" @default.
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• W2073625052 doi "https://doi.org/10.1034/j.1600-0773.2003.930404.x" @default.
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