Astroglia contain a specific transport mechanism for N-acetyl-L-aspartate

N-Acetylaspartate (NAA) is the second most abundant amino acid in the adult brain. It is located and synthesized in neurons and probably degraded in t he glia compartment, but the transport mechanisms are unknown. Rat primary neuron and astrocyte cell cultures were exposed to the L isomer of [H-3]NAA and demonstrated concentration-dependent uptake of [H-3]NAA with a K-m app roximate to 80 mu M. However, V-max was 23 +/- 6.4 pmol/mg of protein/min i n astrocytes but only 1.13 +/- 0.4 pmol/mg of protein/min in neurons. The f act that neuron cultures contain 3-5% astrocytes suggests that the uptake m echanism is expressed only in glial cells. The astrocyte uptake was tempera ture and sodium chloride dependent and specific for L-NAA. The affinity for structural analogues was (IC50 in mM) as follows: L-NAA (0.12) > N-acetyta spartylglutamate (0.4) > N-acetylglutamate (0.42) > L-aspartate (> 1) > L-g lutamate (> 1) greater than or equal to DL-threo-beta-hydroxyaspartate > N- acetyl-L-histidine. The naturally occurring amino acids showed no inhibitor y effect at 1 mM. The glutamate transport blocker trans-pyrrolidine-2,4-dic arboxylate exhibited an IC50 of 0.57 mM, whereas another specific glutamate transport inhibitor, DL-threo-beta-hydroxyaspartate, had an IC50 of >1 mM. The experiments suggest that NAA transport in brain parenchyma occurs by a novel type of sodium-dependent carrier that is present only in glial cells .