Glutamate as a CNS transmitter. II. Regulation of synthesis in the releasable pool

Hamberger, Anders; Chiang, Grace; Sandoval, Elena; Cotman, Carl W.

doi:10.1016/0006-8993(79)90307-x

Cited by 154 publications

(34 citation statements)

References 16 publications

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“…Glu release occurred readily in the presence of calcium, a condition mimicking the brain 'at work' (Hamberger et al, 1979b), and more of the released Glu originated from Gln than from glucose (Hamberger et al, 1979a). Depolarization per se acted as a factor stimulating Gln uptake and its conversion to Glu (Hamberger et al, 1979a) or GABA (Szerb, 1984). The inhibition of PAG, which catalyzes the generation of Glu from Gln in neurons, reduced the synaptosomal pools of Glu and Asp and decreased the depolarizationdependent release of Glu (Bradford et al, 1989).…”

Section: Stimulus-driven Release Of Gln-derived Glu and Gaba From Difmentioning

confidence: 99%

Roles of glutamine in neurotransmission

2010

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Glutamine (Gln) is found abundantly in the central nervous system (CNS) where it participates in a variety of metabolic pathways. Its major role in the brain is that of a precursor of the neurotransmitter amino acids: the excitatory amino acids, glutamate (Glu) and aspartate (Asp), and the inhibitory amino acid, γ-amino butyric acid (GABA). The precursor-product relationship between Gln and Glu/GABA in the brain relates to the intercellular compartmentalization of the Gln/Glu(GABA) cycle (GGC). Gln is synthesized from Glu and ammonia in astrocytes, in a reaction catalyzed by Gln synthetase (GS), which, in the CNS, is almost exclusively located in astrocytes (Martinez-Hernandez et al., 1977). Newly synthesized Gln is transferred to neurons and hydrolyzed by phosphate-activated glutaminase (PAG) to give rise to Glu, a portion of which may be decarboxylated to GABA or transaminated to Asp. There is a rich body of evidence which indicates that a significant proportion of the Glu, Asp and GABA derived from Gln feed the synaptic, neurotransmitter pools of the amino acids. Depolarization-induced-, calcium- and PAG activity-dependent releases of Gln-derived Glu, GABA and Asp have been observed in CNS preparations in vitro and in the brain in situ. Immunocytochemical studies in brain slices have documented Gln transfer from astrocytes to neurons as well as the location of Gln-derived Glu, GABA and Asp in the synaptic terminals. Patch-clamp studies in brain slices and astrocyte/neuron co-cultures have provided functional evidence that uninterrupted Gln synthesis in astrocytes and its transport to neurons, as mediated by specific carriers, promotes glutamatergic and GABA-ergic transmission. Gln entry into the neuronal compartment is facilitated by its abundance in the extracellular spaces relative to other amino acids. Gln also appears to affect neurotransmission directly by interacting with the NMDA class of Glu receptors. Transmission may also be modulated by alterations in cell membrane polarity related to the electrogenic nature of Gln transport or to uncoupled ion conductances in the neuronal or glial cell membranes elicited by Gln transporters. In addition, Gln appears to modulate the synthesis of the gaseous messenger, nitric oxide (NO), by controlling the supply to the cells of its precursor, arginine. Disturbances of Gln metabolism and/or transport contribute to changes in Glu-ergic or GABA-ergic transmission associated with different pathological conditions of the brain, which are best recognized in epilepsy, hepatic encephalopathy and manganese encephalopathy.

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Section: Stimulus-driven Release Of Gln-derived Glu and Gaba From Difmentioning

confidence: 99%

Roles of glutamine in neurotransmission

2010

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“…These transporters are thought to sequester the majority of extracellular Glu released from neurons. In astrocytes, extracellular Glu is incorporated and converted to glutamine by the enzyme specific for astroglia glutamine synthase, and then glutamine is shuttled back to neurons for the synthesis of Glu toward the storage in neurons (13). On this glutamate-glutamine hypothesis for the neurotransmitter compartment, astroglia play an important role in mechanisms underlying the disposition at synaptic vesicles Three different subtypes of VGLUTs are recently characterized in mediation of Glu transport for condensation into synaptic vesicles within the CNS.…”

Section: Glutamate Signaling Moleculesmentioning

confidence: 99%

Glutamate Signaling System in Bone

2004

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Abstract. L-Glutamate (Glu) has been thought to be an excitatory amino acid neurotransmitter in the mammalian central nervous system (CNS). The hypothesis is supported by successful cloning of a number of genes encoding different signaling molecules, such as Glu receptors for signal input, Glu transporters for signal termination, and vesicular Glu transporters for signal output through exocytotic release. Limited information is available in the literature with regard to an extracellular transmitter role of Glu in peripheral neuronal and non-neuronal tissues, whereas recent molecular biological analyses including ours give rise to a novel function for Glu as an autocrine and / or paracrine factor in bone comprised of osteoblasts, osteoclasts, and osteocytes, in addition to other peripheral tissues including pancreas, adrenal, and pituitary glands. Emerging evidence suggests that Glu could play a dual role in mechanisms underlying maintenance of cellular homeostasis as an excitatory neurotransmitter in the CNS and as an extracellular signal mediator in peripheral autocrine and / or paracrine tissues. In this review, therefore, we summarized the possible signaling by Glu as an extracellular signal mediator in mechanisms underlying maintenance of cellular homeostasis with a focus on bone tissues.

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“…Experiments supporting the concept that glutamine is a precursor of transmitter glutamate have been reported using rat brain synaptosomes (Bradford et al, 1978), toad brain hemisections (Shank and Aprison, 1977), and slices from pigeon optic tectum (Reubi et al, 1978), mouse brain cortex (Tapia and Gonzalez, 1978), and dentata gyrus of the hippocampal formation (Hamberger et al, 1979a,b (Bradford et al, 1978), and experiments with single-labeled [ 14 C]glucose and [ 14 C]glutamine, show that the glutamate released by depolarization also, to a great extent, is derived from glucose (Hamberger et al, 1979b).…”

Section: Precursors Of Transmitter Glutamatementioning

confidence: 99%

Synthesis of transmitter glutamate and the glial-neuron interrelationship

Torgner

Kvamme

1990

Molecular and Chemical Neuropathology

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Glutamate in glutamatergic neurons exists in a cytosolic pool, as well as a transmitter pool, which is assumed to be localized in synaptic vesicles. Transmitter glutamate released from glutamatergic neurons is taken up by both neurons and glial cells, giving rise to a flux of glutamate from neurons to astrocytes. In astrocytes, glutamine is formed from glutamate by the glial-specific enzyme glutamine synthetase (EC 6.3.1.2). Glutamine diffuses back to neurons, where glutamate is formed by phosphate-activated glutaminase (EC 3.5.1.2). However, this cycle is not stoichiometric, and glutamine obtained from glial cells cannot replenish all transmitter glutamate lost from neurons. 2-Oxoglutarate is another putative precursor for transmitter glutamate. Net synthesis of citric acid cycle intermediates is dependent on carbon dioxide fixation to pyruvate, catalyzed by pyruvate carboxylase (EC 6.4.1.1). Since this enzyme is exclusively glial, a net flow of citric acid cycle intermediates from glial cells to neurons probably exists. The quantitative contribution of each transmitter precursor may not be the same in different regions of the brain and may vary with the metabolic state of the neuron. The pool of transmitter glutamate is most likely regulated by the activity of glutamate-forming enzymes in the nerve terminal, and/or by uptake/release of glutamate and glutamate precursors through the synaptosomal plasma membrane.

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Glutamate as a CNS transmitter. II. Regulation of synthesis in the releasable pool

Cited by 154 publications

References 16 publications

Roles of glutamine in neurotransmission

Roles of glutamine in neurotransmission

Glutamate Signaling System in Bone

Synthesis of transmitter glutamate and the glial-neuron interrelationship

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