In Vivo Release from Cerebral Cortex of [14C]Glutamate Synthesized from [U‐14C]Glutamine

Thanki, C. M.; Sugden, David; Thomas, Alan; Bradford, H. F.

doi:10.1111/j.1471-4159.1983.tb04785.x

Cited by 93 publications

(47 citation statements)

References 18 publications

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“…As reported in the Introduction, a large body of experimental data obtained by a variety of methods supports the notion that PAG is a crucial although not exclusive enzyme for the synthesis of transmitter Glu (Ji et al, 1991;Sherman and Mott, 1986;Thanki et al, 1983;Ward et al, 1983;Reubi, 1980;Hamberger et al, 1979a,b;Hertz, 1979;Bradford et al, 1978Bradford et al, ,1983. These data have been recently confirmed by showing an elevation of KCI-and 4-aminopyridine-induced Glu release from synaptosomal preparations pre-incubated with glutamine (Sherman, 1991).…”

Section: Discussionmentioning

confidence: 77%

“…Several biosynthetic pathways are believed to produce releasable Glu: glutamine, tricarboxylic acid cycle constituents (such as a-ketoglutarate and malate), ornithine, and glucose (Erecinska and Silver, 1990;Hertz and Schousboe, 1988;Shank and Aprison, 1988;Fonnum, 1984), but their relative contributions are still incompletely understood. Many studies, however, strongly suggest that the conversion of glutamine (Gln) to Glu catalyzed by phosphate-activated glutaminase (EC 3.5.1.2; PAG) plays a crucial role in the formation of releasable Glu (Ji et al, 1991;Sherman and Mott, 1986;Thanki et al, 1983;Reubi, 1980;Hamberger et al, 1979a.b;Hertz, 1979;Reubi et al, 1978;Bradford et al, 1978Bradford et al, ,1983. It has been calculated that PAG activity seems to be responsible for up to 75% of the Glu released in a calciumdependent manner (Hamberger et al, 1979a,b).…”

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confidence: 99%

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Glutamate immunoreactivity in rat cerebral cortex is reversibly abolished by 6-diazo-5-oxo-L-norleucine (DON), an inhibitor of phosphate-activated glutaminase.

Conti¹,

Minelli²

1994

J Histochem Cytochem.

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Glutamate (Glu) immunocytochemistry has been widely used to identify presumed gluergic neurons and synapses, but several problems related to the fact that Glu is both a synaptic transmitter and a compound used for metabolic purposes are d unsolved. One of these concerns the intease perikarllal staining observed in perfusion-fued tissue. Phosphateactivated glutaminase, a key enzyme for the synthesis of releasable glutamate, is inhibited by the diazoketone 6-diazo-5-oxo-~-norleucine (DON), which greatly reduces glutamate release. In the ptesent experiments, DON was either injected intraparenchymally or applied epipially to the sensorimotor cortex of adult Sprague-Dawley rats at concentrations of 0.25-1 mM. Both intrapenchymal and epipial applications of the chemical abolished Glu immunoreactivity in neuron IntroductionThe acidic amino acid glutamate (Glu) is the major excitatory neurotransmitter in the mammalian brain (Shank and Aprison, 1988;Fonnum, 1984) and has been implicated in diverse physiological and pathological processes, such as developmental and use-dependent plasticity, long-term potentiation, neurotoxicity, and degenerative disorders (Meldrum and Garthwaite, 1990;Choi, 1988;Artola and Singer, 1987, 1989;Bear et al., 1987). Understanding of the mechanisms by which Glu plays its role in these processes requires not only the detailed knowledge of the postsynaptic receptors implicated and of the biochemical events that follow the interaction between Glu and its receptors but also the identification of presynaptic neurons and axon terminals.A major advance in the persistent search for an anatomic method capable of visualizing glutamatergic (Glu-ergic) neurons and synapses occurred in 1983, when it was shown that neurons and axon terminals containing high levels of Glu could be studied by using immunocytochemical techniques (Storm-Mathisen et al., 1983 This approach has since become widely used to study the chemical anatomy of presumptive Glu-ergic neurons, synapses, and pathways in many central nervous system (CNS) structures (for review see Petrusz and Rustioni, 1989). Several studies have now clearly established that both pre-and post-embedding electron microscopy of sections immunocytochemically stained with anti-Glu sera are reliable tools for studying Glu-ergic axon terminals (DeBiasi and Rustioni, 1990;Conti et al., 1989;Dori et al., 1989;DeFelipe et al., 1988;Ottersen, 1987Ottersen, ,1989. However, the suitability of Glu immunostaining as a reliable indicator of Glu-ergic neurons is a subject of considerable debate, since the main light microscopic feature of pre-embedding Glu immunostaining of perfusion-fixed tissue is the presence of intense perikaryal labeling (e.g., Conti et al., 1987a;Ottersen and Storm-Mathisen, 1984), an observation that is apparently hardly reconcilable with the widely accepted notion that transmitter Glu is synthesized at the nerve terminal (Fonnum, 1991). In their review, Petrusz and Rustioni (1989) wrote: "It seems prudent to regard strong and consistent staining in neu...

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Section: Discussionmentioning

confidence: 77%

mentioning

confidence: 99%

Glutamate immunoreactivity in rat cerebral cortex is reversibly abolished by 6-diazo-5-oxo-L-norleucine (DON), an inhibitor of phosphate-activated glutaminase.

Conti¹,

Minelli²

1994

J Histochem Cytochem.

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“…The Glt-Gln cycle is the major metabolic pathway of both Glt and Gln in the brain (Kanamori et al, 2002;Thanki et al, 1983). Other pathways however also exist, which may have influenced our results.…”

Section: Discussionmentioning

confidence: 88%

Cerebral Glutamine and Glutamate Levels in Relation to Compromised Energy Metabolism: A Microdialysis Study in Subarachnoid Hemorrhage Patients

Samuelsson

Hillered

Zetterling

et al. 2007

J Cereb Blood Flow Metab

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Astrocytic glutamate (Glt) uptake keeps brain interstitial Glt levels low. Within the astrocytes Glt is converted to glutamine (Gln), which is released and reconverted to Glt in neurons. The Glt-Gln cycle is energy demanding and impaired energy metabolism has been suggested to cause low interstitial Gln/Glt ratios. Using microdialysis (MD) measurements from visually noninjured cortex in 33 neurointensive care patients with subarachnoid hemorrhage, we have determined how interstitial Glt and Gln, as a reflection of the Glt-Gln cycle turnover, relate to perturbed energy metabolism. A total of 3703 hourly samples were analyzed. The lactate/pyruvate (L/P) ratios correlated to the Gln/Glt ratios (r = À0.66), but this correlation was not stronger than the correlation between L/P and Glt (r = 0.68) or the correlation between lactate and Glt (r = 0.65). A novel observation was a linear relationship between interstitial pyruvate and Gln (r = 0.52). There were 13 periods (404 h) of 'energy crisis', defined by L/P ratios above 40. All were associated with high interstitial Glt levels. Periods with L/P ratios above 40 and low pyruvate levels were associated with decreased interstitial Gln levels, suggesting ischemia and failing astrocytic Gln synthesis. Periods with L/P ratios above 40 and normal or high pyruvate levels were associated with increased interstitial Gln levels, which may represent an astrocytic hyperglycolytic response to high interstitial Glt levels. The results imply that moderately elevated L/P ratios cannot always be interpreted as failing energy metabolism and that interstitial pyruvate levels may discriminate whether or not there is sufficient astrocytic capacity for Glt-Gln cycling in the brain.

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“…In the case of the major excitatory transmitter glutamate, however, the known plasma membrane transporters generally reside either postsynaptically or on glia (39,40). Indeed, glutamate has been proposed to recycle through astrocytes (41)(42)(43), undergoing conversion to glutamine by the enzyme glutamine synthetase after uptake from the synapse (44). Glutamine is then released from the glia and taken up by neurons before conversion back to glutamate.…”

Section: Discussionmentioning

confidence: 99%

Amino acid transport System A resembles System N in sequence but differs in mechanism

Reimer

Chaudhry

Gray

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

179

138

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Classical amino acid transport System A accounts for most of the Na ؉ -dependent neutral amino acid uptake by mammalian cells. System A has also provided a paradigm for short-and long-term regulation by physiological stimuli. We now report the isolation of a cDNA encoding System A that shows close similarity to the recently identified System N transporter (SN1). The System A transporter (SA1) and SN1 share many functional characteristics, including a marked sensitivity to low pH, but, unlike SN1, SA1 does not mediate proton exchange. Transport mediated by SA1 is also electrogenic. Amino acid transport Systems A and N thus appear closely related in function as well as structure, but exhibit important differences in ionic coupling.

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In Vivo Release from Cerebral Cortex of [¹⁴C]Glutamate Synthesized from [U‐¹⁴C]Glutamine

Cited by 93 publications

References 18 publications

Glutamate immunoreactivity in rat cerebral cortex is reversibly abolished by 6-diazo-5-oxo-L-norleucine (DON), an inhibitor of phosphate-activated glutaminase.

Glutamate immunoreactivity in rat cerebral cortex is reversibly abolished by 6-diazo-5-oxo-L-norleucine (DON), an inhibitor of phosphate-activated glutaminase.

Cerebral Glutamine and Glutamate Levels in Relation to Compromised Energy Metabolism: A Microdialysis Study in Subarachnoid Hemorrhage Patients

Amino acid transport System A resembles System N in sequence but differs in mechanism

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