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Oral L‐glutamine increases GABA levels in striatal tissue and extracellular fluid
Author(s) -
Wang Lei,
Maher Timothy J.,
Wurtman Richard J.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-7495com
Subject(s) - glutamine , microdialysis , glutamate receptor , gabaergic , chemistry , medicine , striatum , endocrinology , glutamine synthetase , extracellular , pharmacology , biochemistry , biology , amino acid , dopamine , receptor
We explored the possibility that circulating glutamine affects γ‐aminobutyric acid (GABA) levels in rat striatal tissue and GABA concentrations in striatal extracellular fluid (ECF). Striatal microdialy‐sates, each collected over a 20 min interval, were obtained after no treatment, oral L ‐glutamine (0.5 g/kg), or glutamine followed by NMDA (administered via the microdialysis probe). GABA concentrations were measured by HPLC using a stable OPA/sulfite precolumn derivatization and an electrochemical detection method. L ‐Glutamine administration significantly increased ECF GABA concentrations by 30%, and en‐hanced the response evoked by NMDA alone (70%) to 120% over baseline (all P <0.05). Striatal GABA levels increased significantly 2.5 h after oral L ‐glutamine (e.g. , from 1.76 ± 0.04 μmol/g in vehicle‐treated rats to 2.00 ± 0.15 μmol/g in those receiving 2.0 g/kg of glutamine). Striatal glutamine levels also increased significantly, but not those of glutamate. These data suggest that GABA synthesis in, and release from, rat striatum may be regulated in part by circulating glu‐tamine. Hence, glutamine administration may provide a useful adjunct for treating disorders (e.g. , anxiety, seizures) when enhanced GABAergic transmission is desired. Moreover, the elevation in plasma and brain glutamine associated with hepatic failure may, by increasing brain GABA release, produce some of the manifestations of hepatic encephalopathy.—Wang, L., Maher, T. J., Wurtman, R. J. Oral L‐glutamine increases GABA levels in striatal tissue and extracellular fluid. FASEB J. 21, 1227–1232 (2007)