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

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.

journal_name

J Neurochem

authors

Tetsuka K,Takanaga H,Ohtsuki S,Hosoya K,Terasaki T

doi

10.1046/j.1471-4159.2003.02063.x

keywords:

subject

Has Abstract

pub_date

2003-11-01 00:00:00

pages

891-901

issue

4

eissn

0022-3042

issn

1471-4159

pii

2063

journal_volume

87

pub_type

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