Regulation of the Na+-Dependent Glutamate/Aspartate Transporter in Rodent Cerebellar Astrocytes |
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Authors: | Alfonso Bernabé J Alfredo Méndez L Clara R Hernández-Kelly Arturo Ortega |
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Institution: | (1) Departamento de Genética y Biología Molecular, Cinvestav-IPN, Apartado Postal 14-740, México, D.F., 07000, México |
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Abstract: | The regulation of the Na+-dependent glutamate/aspartate transporter system GLAST expressed in rat and mouse cerebellar and cortical astrocytic cultures was examined. Pretreatment of the cerebellar cells with l-glutamate and 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a known Ca2+/ diacylglicerol-dependent protein kinase (PKC) activator, produced a decrease in 3H]-d-aspartate uptake. This reduction was dose- and time-dependent and sensitive to PKC inhibitors. Furthermore, the l-glutamate–dependent 3H]-d-aspartate uptake decrease is a non-receptor dependent process, because neither of the agonists or antagonists were effective in mimicking or reverting the effect. Interestingly, transportable substrates could reproduce the l-glutamate effect. In sharp contrast, in cortical astrocytes, both l-glutamate and TPA pre-exposure result in an augmentation of the 3H]-d-aspartate uptake. These findings suggest that the Na+-dependent glutamate uptake GLAST undergoes a region-specific regulation. |
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Keywords: | GLAST cerebellum astrocytes glutamate uptake signal transduction |
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