Transports of Excitatory and Inhibitory Neurotransmitters Across the Blood-brain Barrier.

Accession number;00A0997676
Title;Transports of Excitatory and Inhibitory Neurotransmitters Across the Blood-brain Barrier.
Author; TAKANAGA HITOMI (Kagakugijutsushinkojigyodan Crest) TETSUKA KAZUHIRO (Tohoku Univ., Fac. of Pharm.) ASABA HIROSHI (Tohoku Univ., Fac. of Pharm.) OTSUKI SUMIO (Kagakugijutsushinkojigyodan Crest) HOSOYA KEN'ICHI (Kagakugijutsushinkojigyodan Crest) TERASAKI TETSUYA (Kagakugijutsushinkojigyodan Crest)
Journal Title;Xenobiotic Metabolism and Disposition
Journal Code:X0758A
ISSN:0916-1139
VOL.15;NO.Supplement;PAGE.S102-S103(2000)
Figure&Table&Reference;FIG.2, REF.3
Pub. Country;Japan
Language;Japanese
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 transporter's 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 0.0346min-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.MU.M 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. (author abst.)