Effect of intracellular glutamine on the uptake of large neutral amino acids in astrocytes: concentrative Na(+)-independent transport exhibits metastability.

Abstract:

:To examine whether the concentration gradient of glutamine (Gln) drives concentrative Na(+)-independent uptake of neutral amino acids (NAA) in mouse cerebral astrocytes, uptake was compared in "Gln-depleted" and "Gln-replete" cultures. Uptake (30 min in Na(+)-free buffer) of histidine, kynurenine, leucine, tyrosine, and a model substrate for System L transport was 70-150% greater in Gln-replete cultures. Phenylalanine uptake was not affected. All of these NAA trans-stimulated the export of Gln from astrocytes. However, the increase in NAA uptake was sustained even though the Gln content of Gln-replete cultures declined. Also, uptake of Gln itself was enhanced in Gln-replete cultures. Thus, countertransport of Gln was insufficient to explain the enhancement of NAA uptake. Enhanced uptake was restored, and could be magnified, by reloading Gln-depleted cultures either with Gln or with histidine. It is suggested that substrate-induced asymmetry and molecular hysteresis in the Na(+)-independent carrier could account for the sustained enhancement of NAA uptake. Only histidine and kynurenine were concentrated comparably to Gln (15- to 29-fold at 1 mM in Na(+)-free buffer). The other NAA were four to six times less concentrated. At least two Na(+)-dependent transport systems also supported the concentration gradient of Gln in regular buffer.

journal_name

J Neurochem

authors

Brookes N

doi

10.1111/j.1471-4159.1992.tb08895.x

keywords:

subject

Has Abstract

pub_date

1992-07-01 00:00:00

pages

227-35

issue

1

eissn

0022-3042

issn

1471-4159

journal_volume

59

pub_type

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