Abstract
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 microdialysates, 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 enhanced 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 glutamine. 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1227-1232 |
| Number of pages | 6 |
| Journal | FASEB Journal |
| Volume | 21 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2007 |
| Externally published | Yes |
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Keywords
- Glutamate
- Hepatic encephalopathy
- Microdialysis
- Neurotransmitter precursor
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics
Cite this
Oral L-glutamine increases GABA levels in striatal tissue and extracellular fluid. / Wang, Lei; Maher, Timothy J.; Wurtman, Richard J.
In: FASEB Journal, Vol. 21, No. 4, 01.04.2007, p. 1227-1232.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Oral L-glutamine increases GABA levels in striatal tissue and extracellular fluid
AU - Wang, Lei
AU - Maher, Timothy J.
AU - Wurtman, Richard J.
PY - 2007/4/1
Y1 - 2007/4/1
N2 - 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 microdialysates, 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 enhanced 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 glutamine. 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.
AB - 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 microdialysates, 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 enhanced 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 glutamine. 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.
KW - Glutamate
KW - Hepatic encephalopathy
KW - Microdialysis
KW - Neurotransmitter precursor
UR - http://www.scopus.com/inward/record.url?scp=33947656412&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33947656412&partnerID=8YFLogxK
U2 - 10.1096/fj.06-7495com
DO - 10.1096/fj.06-7495com
M3 - Article
C2 - 17218538
AN - SCOPUS:33947656412
VL - 21
SP - 1227
EP - 1232
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 4
ER -