N‐System Amino Acid Transport at the Blood‐CSF Barrier

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Abstract
Despite l‐glutamine being the most abundant amino acid in CSF, the mechanisms of its transport at the choroid plexus have not been fully elucidated. This study examines the role of L‐, A‐, ASC‐, and N‐system amino acid transporters in l‐[14C]glutamine uptake into isolated rat choroid plexus. In the absence of competing amino acids, approximately half the glutamine uptake was via a Na+‐dependent mechanism. The Na+‐independent uptake was inhibited by 2‐amino‐2‐norbornane carboxylic acid, indicating that it is probably via an L‐system transporter. Na+‐dependent uptake was inhibited neither by the A‐system substrate α‐(methylamino)isobutyric acid nor by the ASC‐system substrate cysteine. It was inhibited by histidine, asparagine, and l‐glutamate γ‐hydroxamate, three N‐system substrates. Replacement of Na+ with Li+ had little effect on uptake, another feature of N‐system amino acid transport. These data therefore indicate that N‐system amino acid transport is present at the choroid plexus. The Vmax and Kmax for glutamine transport by this system were 8.1 ± 0.3 nmol/mg/min and 3.3 ± 0.4 mM, respectively. This system may play an important role in the control of CSF glutamine, particularly when the CSF glutamine level is elevated as in hepatic encephalopathy.

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