Glutamine and glutamate as precursors of the releasable pool of gaba in brain cortex slices

Tapia, Ricardo; Gonzalez, Rosa Maria

doi:10.1016/0304-3940(78)90029-0

Cited by 75 publications

(29 citation statements)

References 19 publications

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“…3 and 4), 4-deoxypyridoxine or isoniazid (data not shown). Glutamine has been reported to be a precursor of the GABA transmitter pool (Tapia and Gonzales, 1978;Kernel et aL, 1979;Reubi, 1980). Our data support this notion although it must be studied more in detail.…”

Section: Discussionsupporting

confidence: 89%

Effect of the normal nerve impulse flow on the synthesis and utilization of GABA in the rat substantia nigra

Lindgren¹,

Andén²

1985

J. Neural Transmission

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The concentrations of GABA, glutamate, serine, glutamine, threonine, glycine and taurine in the substantia nigra and in the corpus striatum of the rat were determined electrochemically following condensation with o-phthalaldehyde-beta-mercaptoethanol and reverse-phase, high performance liquid chromatography. After a frontal hemisection at the level of the caudal hypothalamus, the GABA concentration in the substantia nigra on the operated side decreased to about 20 per cent of the normal value in 4 days, in all probability caused by degeneration of the nerve terminals of the striato-nigral GABA neurons. The concentrations of taurine in the substantia nigra and of GABA in the corpus striatum were initially lowered and later elevated following this lesion. The concentration of glutamate in the substantia nigra was lower on the sectioned side and higher on the intact side at 14 days as compared to 4 hours after a hemisection. Following an acute hemisection, the GABA transaminase inhibitor gamma-acetylenic GABA increased the concentration of GABA by 36% and 79% in the substantia nigra on the sectioned and intact side, respectively. The glutamate decarboxylase inhibitors 4-deoxypyridoxine and isoniazid lowered the concentration of GABA in the substantia nigra by about 50% on both the sectioned and intact side. The results indicate that the synthesis, but not the utilization of GABA in the substantia nigra is dependent on the normal nerve impulse flow. The concentration of glutamine was changed in directions contrary to that of GABA following a chronic hemisection or treatment with gamma-acetylenic GABA, in agreement with the suggestion that glutamine is a precursor of the GABA transmitter pool.

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Section: Discussionsupporting

confidence: 89%

Effect of the normal nerve impulse flow on the synthesis and utilization of GABA in the rat substantia nigra

Lindgren¹,

Andén²

1985

J. Neural Transmission

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“…Glutamine is a major precursor of glutamate and GABA (Lebon et al 2002;Patel et al 2001;Paulsen et al 1988;Peng et al 1993;Tapia and González 1978). A crucial step in the glutamate-glutamine cycle is the astrocytic release of glutamine into the extracellular space (Chaudhry et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Maintenance of Thalamic Epileptiform Activity Depends on the Astrocytic Glutamate-Glutamine Cycle

Bryant

Beenhakker

et al. 2009

Journal of Neurophysiology

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Bryant AS, Li B, Beenhakker MP, Huguenard JR. Maintenance of thalamic epileptiform activity depends on the astrocytic glutamateglutamine cycle. J Neurophysiol 102: 2880 -2888, 2009. First published September 9, 2009 doi:10.1152/jn.00476.2009. The generation of prolonged neuronal activity depends on the maintenance of synaptic neurotransmitter pools. The astrocytic glutamate-glutamine cycle is a major mechanism for recycling the neurotransmitters GABA and glutamate. Here we tested the effect of disrupting the glutamateglutamine cycle on two types of neuronal activity patterns in the thalamus: sleep-related spindles and epileptiform oscillations. In recording conditions believed to induce glutamine scarcity, epileptiform oscillations showed a progressive reduction in duration that was partially reversible by the application of exogenous glutamine (300 M). Blocking uptake of glutamine into neurons with ␣-(methylamino) isobutyric acid (5 mM) caused a similar reduction in oscillation duration, as did blocking neuronal GABA synthesis with 3-mercaptoproprionic acid (10 M). However, comparable manipulations did not affect sleep spindles. Together, these results support a crucial role for the glutamate-glutamine cycle in providing the neurotransmitters necessary for the generation of epileptiform activity and suggest potential therapeutic approaches that selectively reduce seizure activity but maintain normal neuronal activity.

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“…Glutamine, which is a good precursor for GABA in vitro (e.g., Tapia and Gonzalez, 1978), can probably account for only 60 -70% of the GABA formation in the brain (Hassel et al, 1998). Therefore pyruvate carboxylation may have an important role in GABAergic neurons.…”

Section: Pyruvate Carboxylation In Gabaergic Neurons?mentioning

confidence: 99%

Pyruvate carboxylation in neurons

Hassel

2001

J of Neuroscience Research

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Carboxylation of pyruvate in the brain was for many years thought to occur only in glia, an assumption that formed much of the basis for the concept of the glutamine cycle. It was shown recently, however, that carboxylation of pyruvate to malate occurs in neurons and that it supports formation of transmitter glutamate. The role of pyruvate carboxylation in neurons is to ensure tricarboxylic acid cycle activity by compensating for losses of alpha-ketoglutarate that occur through release of transmitter glutamate and GABA; these amino acids are alpha-ketoglutarate derivatives. Available data suggest that neuronal pyruvate carboxylation is quantitatively important. But because there is no net CO(2) fixation in the brain, pyruvate carboxylation must be balanced by decarboxylation of malate or oxaloacetate. Such decarboxylation occurs in both neurons and astrocytes. Several in vitro studies have shown a neuroprotective effect of pyruvate supplementation. Pyruvate carboxylation may be one mechanism through which such treatment is effective, because pyruvate carboxylation through malic enzyme is active during energy deficiency and leads to an increase in the level of dicarboxylates that can be metabolized through the tricarboxylic acid cycle for ATP production.

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Glutamine and glutamate as precursors of the releasable pool of gaba in brain cortex slices

Cited by 75 publications

References 19 publications

Effect of the normal nerve impulse flow on the synthesis and utilization of GABA in the rat substantia nigra

Effect of the normal nerve impulse flow on the synthesis and utilization of GABA in the rat substantia nigra

Maintenance of Thalamic Epileptiform Activity Depends on the Astrocytic Glutamate-Glutamine Cycle

Pyruvate carboxylation in neurons

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