The L-isomer-selective transport of aspartic acid is mediated by ASCT2 at the blood-brain barrier

Kazuhiro Tetsuka, Hitomi Takanaga, Sumio Ohtsuki, Ken Ichi Hosoya, Tetsuya Terasaki

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Aspartic acid (Asp) undergoes L-isomer-selective efflux transport across the blood-brain barrier (BBB). This transport system appears to play an important role in regulating L- and D-Asp levels in the brain. The purpose of this study was to identify the responsible transporters and elucidate the mechanism for L-isomer-selective Asp transport at the BBB. The L-isomer-selective uptake of Asp by conditionally immortalized mouse brain capillary endothelial cells used as an in vitro model of the BBB took place in an Na+- and pH-dependent manner. This process was inhibited by system ASC substrates such as L-alanine and L-serine, suggesting that system ASC transporters, ASCT1 and ASCT2, are involved in the L-isomer selective transport. Indeed, L-Asp uptake by oocytes injected with either ASCT1 or ASCT2 cRNA took place in a similar manner to that in cultured BBB cells, whereas no significant D-Asp uptake occurred. Although both ASCT1 and ASCT2 mRNA were expressed in the cultured BBB cells, the expression of ASCT2 mRNA was 6.7-fold greater than that of ASCT1. Moreover, immunohistochemical analysis suggests that ASCT2 is localized at the abluminal side of the mouse BBB. These results suggest that ASCT2 plays a key role in L-isomer-selective Asp efflux transport at the BBB.

Original languageEnglish
Pages (from-to)891-901
Number of pages11
JournalJournal of Neurochemistry
Volume87
Issue number4
DOIs
Publication statusPublished - 2003 Nov 1

Keywords

  • ASCT
  • Amino acid transporter
  • Aspartic acid
  • Blood-brain barrier
  • Brain capillary endothelial cells
  • Isomer-selective

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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