GLUTAMINE UPTAKE AT THE BLOOD-BRAIN-BARRIER IS MEDIATED BY N-SYSTEM TRANSPORT

The mechanism of unidirectional transport of glutamine from blood to b rain in pentobarbital-anesthetized rats was examined using in situ per fusion. Amino acid uptake into brain across the blood-brain barrier (B BB) is classically thought to be via the Na-independent large neutral (L-system), acidic and basic amino acid transporters. In the presence of physiological concentrations of amino acids in the perfusate, which should saturate the known amino acid transporters at the BBB, the cor tical transfer constant (K-i) for L-[C-14]glutamine was 11.6 +/- 1.1 m u l/g/min. The addition of either 10 mM 2-amino-2-norbornanecarboxylic acid or 10 mM 2-amino-2-norbornanecarboxylic acid and 5 mM cysteine h ad no effect on the cortical K-i for L-[14C]glutamine, indicating that glutamine transport under these conditions does not occur by the L-, A-, or ASC-systems. Decreasing perfusate Na from 140 to 2.4 mM by Tris substitution reduced the cortical K-i for L-[C-14]glutamine by 62% (p less than or equal to 0.001). The Na-dependent uptake has the charact eristics of L-system transport. It was inhibited by L-histidine and L- glutamine, both N-system substrates, and it was pH sensitive and moder ately tolerant of Li substitution for Na. This putative N-system trans porter at the luminal membrane of the BBB plays an important role in m ediating brain glutamine uptake.