Uptake of Glutamate and Cystine in C‐6 Glioma Cells and in Cultured Astrocytes

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Abstract
The uptake of glutamate in rat glioma C-6 cells and cultured astrocytes derived from rat cerebral hemispheres was found to be mediated by a Na+-dependent and a Na+-independent system. The Na+-dependent system was inhibited by aspartate and was consistent with the commonly occurring system designated system X−ag. The Na+-independent system was inhibited by cystine and was consistent with system x−c described in various types of cells in the periphery. It was also found that quisqualate selectively and competitively interfered with the Na+-independent glutamate uptake. In C-6 cells, the glutamate uptake via systems X−ag and x−c accounted for approximately 35% and 55% of the total uptake, respectively, at 0.05 mM glutamate. In cultured astrocytes, the glutamate uptake via system X−ag was very potent, whereas the uptake via system x−c was relatively weak and its contribution to the total uptake of glutamate seemed almost negligible. However, in both C-6 cells and astrocytes, system x−c was necessary for the uptake of cystine, another substrate of system x−c. Cystine in the culture medium was an essential precursor of glutathione, and the inhibition of the cystine uptake by excess glutamate as a competitor led to a severe deficiency in glutathione, followed by cell degeneration.