Oral L‐glutamine increases GABA levels in striatal tissue and extracellular fluid

Abstract

We explored the possibility that circulating glutamine affects gamma-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 micromol/g in vehicle-treated rats to 2.00 +/- 0.15 micromol/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.

Glutamine and glutamic acid enhance thyroid-stimulating hormone β subunit mRNA expression in the rat pars tuberalis

“…5 to 1 . 0 mM and may change in certain physiological states (Wang et al 2007). Therefore, the 1 mM concentrations of glutamine used in this study are reasonable and reflect the physiological conditions in vivo.…”

“…07-0 . 1 mM in the plasma; Hawkins et al 1995, Wang et al 2007, which indicates that circulating glutamic acid does not physiologically interact with GluRs. In general, glutamic acid is locally converted by Gls from glutamine, which is absorbed into the cell via glutamine transporters (de la Rosa et al 2009), acts as an autocrine and/or paracrine neurotransmitter in the CNS, and functions as an extracellular signal mediator in the peripheral tissues (Hinoi et al 2004).…”

The effect of omega-3 on cognition in hypothyroid adult male rats

“…The hippocampus was dissected and weighed then immediately frozen using liquid nitrogen and finally stored at -80 °C until being assayed for serotonin and GABA. GABA and serotonin contents were measured by high performance liquid chromatography (HPLC) with fluorescence detection (Agilent 1200 series) as described previously (45,57). Briefly, for GABA, samples were homogenized in 1 ml (400 mM) HClO 4 and 1 ml EDTA (50 µM), neutralized with borate buffer (100 mM) and centrifuged at 14000 rpm for 15 min at 4° C. A 0.4 ml supernatants with 0.2 ml working solution (orthophthalaldehyde (OPA)/sulfite working reagent) were mixed and after 20 min directly injected to the Zorbax 300 SB-C18 column (4.6 mm × 250 mm, 5 μm) under the following conditions: The mobile phase consisted of 1 mM disodium hydrogen phosphate buffer, flow rate 1 ml/min and the fluorescence excitation and emission wavelengths were set at λex 340 and λem 456 nm, respectively.…”

Intrahippocampal glutamine administration inhibits mTORC1 signaling and impairs long-term memory

“…In addition to influencing mTORC1 activity, glutamine is a precursor used in the synthesis of the neurotransmitters glutamate, aspartate, and GABA (Wang et al 2007;Albrecht et al 2010). It has been previously shown that glutamine can play an important role in regulating synaptic signaling, having impacts on both excitatory (Albrecht et al 2010;Uwechue et al 2012;Tani et al 2014) and inhibitory (Liang et al 2006;Wang et al 2007) synaptic signaling through its effects on glutamate and GABA synthesis and release. As shown in Figure 1, we did not observe any significant change in the overall hippocampal levels of glutamate or aspartate 30 min post-glutamine infusion, although changes in the synaptic levels of these neurotransmitters could not be excluded.…”

“…Since glutamine can also be converted into g-amino butyric acid (GABA) to influence inhibitory signaling (Wang et al 2007), we also examined the effect of increased glutamine on inhibitory postsynaptic currents (IPSCs). Evoked disynaptic GABA A -mediated IPSCs were recorded in the absence of glutamate receptor antagonists by holding postsynaptic CA1 neurons at 0 mV and stimulating Schaffer collaterals.…”