Glutamine transport in C6 glioma cells

Glutamine transport across the cell membranes of a variety of mammalian tis sues is mediated by at least four transport systems: a sodium-independent s ystem L, and sodium-dependent systems A, ASC and N, the latter occurring in different tissue-specific variants. In this study we assessed the contribu tion of these systems to the uptake of [H-3]glutamine in C6 rat glioma cell s. The sodium-dependent uptake, which accounted for more than 80% of the to tal uptake, was not inhibited by 2-methylaminoisobutyric acid (MeAIB), indi cating that system A was inactive, possibly being depressed by glutamine pr esent in the culture medium. About 80% of the sodium-dependent uptake was m ediated by system ASC, which differed from system ASC common to other CNS- and non-CNS tissues by its pH-dependence and partial lithium tolerance. The residual 20% of sodium-dependent uptake appeared to be mediated by system N, which was identified as a component resistant to inhibition by MeAIB + t hreonine. The system N in CS cells appeared to be neither fully compatible with the neuronal system Nb, nor with the N system described in astrocytes: it differed from the former in being strongly inhibited by histidine and s howing fair tolerance for lithium, and from the latter in its pH-insensitiv ity and strong inhibition by glutamate. The sodium-independent glutamine up take differed from the astrocytic or neuronal uptake in its relatively weak inhibition by system L substrates and a strong inhibition by system ASC su bstrates, indicating a possible contribution of a variant of the ASC system . (C) 2000 Elsevier Science Ltd. All rights reserved.