Abstract
Gamma aminobutyric acid (GABA) and acidic amino acids act as the predominant suppressive and excitatory neurotransmitter in the brain, respectively, and are widely distributed over the central nervous system (CNS). For GABA transport, the initial uptake rate of [3H]-GABA by TM-BBB was sodium- and chloride-dependent as well as being concentration-dependent. Its initial uptake was inhibited by the several GABA transporters inhibitors. RT-PCR analysis showed that GAT2/BGT1 was predominantly expressed in the GAT isoforms. For acidic amino acid transport, the efflux rate constants of [3H]L-Asp and [3H]L-Glu from brain across the BBB were 0.207 and 0.0346 min-1, respectively. [3H]D-Asp was not eliminated from the brain over a 20-min period. The initial uptake rate of [3H]L-Asp by TM-BBB was sodium- dependent as well as being concentration-dependent. Its initial uptake was not observed the self-inhibition at 600 μM unlabeled compounds, therefore, [3H]L-Asp was mainly transported via any other transporter rather than EAAT1 ?? 3 at the BBB. These BBB transport may partially regulate the brain distribution and control their brain interstitial fluid concentration by supporting both glial and neuronal transporters.
