Differences between substrate specificities of l-glutamate uptake by neurons and glia, studied in cell lines and primary cultures.

High affinity uptake of [(3)H]l-glutamate was studied in cultures of continuous cell lines, originating either from mouse neuroblastoma or rat glioma, and in two types of primary cultures containing cerebellar granule cells and astrocytes from cerebral cortex, respectively. In the continuous lines, d- and l-aspartate-4-hydroxamate were found to interact preferentially with the uptake of [(3)H]l-glutamate in glioma cells while l-glutamate-5-hydroxamate and 2-aminoadipate interacted more strongly with [(3)H]l-glutamate uptake in neuroblastoma cells, d-Aspartate-4-hydroxyamate, l-glutamate-5-hydroxamate and 2-aminoadipate were inactive as inhibitors of [(3)H]l-glutamate uptake by either granule cells or astrocytes, grown in primary culture, but several other glutamate analogues, which did not differentiate between neuroblastomal and gliomal uptake of [(3)H]l-glutamate, were somewhat stronger inhibitors of [(3)H]l-glutamate uptake in astrocytes as compared to that in granule cells. However, all of these compounds (N-acetyl-l-glutamate, formimino-l-aspartate, d-homocysteate, l-homocysteate and dl-2-methylglutamate) were only very weak inhibitors and, consequently, it is unlikely that any of them could be useful in experiments with central nervous tissue in vivo or, at least, in brain slices in vitro, attempting to resolve the uptake of l-glutamate into glia- and neuron-localized components.