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At least 19 recordsLinked to original sources
PubMed1980

Fate of glutamate carbon and nitrogen in isolated guinea-pig kidney-cortex tubules. Evidence for involvement of glutamate dehydrogenase in glutamine sythesis from glutamate.

1. The pathways and the fate of glutamate carbon and nitrogen were investigated in isolated guinea-pig kidney-cortex tubules. 2. At low glutamate concentration (1 mM), the glutamate carbon skeleton was either completely oxidized or converted into glutamine. At high glutamate concentration (5 mM), glucose, lactate and alanine were additional products of glutamate metabolism. 3. At neither concentration of glutamate was there accumulation of ammonia. 4. Nitrogen-balance calculations and the release of 14CO2 from L-[1-14C]glutamate (which gives an estimation of the flux of glutamate carbon skeleton through alpha-oxoglutarate dehydrogenase) clearly indicated that, despite the absence of ammonia accumulation, glutamate metabolism was initiated by the action of glutamate dehydrogenase and not by transamination reactions as suggested by Klahr, Schoolwerth & Bourgoignie [(1972) Am. J. Physiol. 222, 813-820] and Preuss [(1972) Am. J. Physiol. 222, 1395-1397]. Additional evidence for this was obtained by the use of (i) amino-oxyacetate, an inhibitor of transaminases, which did not decrease glutamate removal, or (ii) L-methionine DL-sulphoximine, an inhibitor of glutamine synthetase, which caused an accumulation of ammonia from glutamate. 5. Addition of NH4Cl plus glutamate caused an increase in both glutamate removal and glutamine synthesis, demonstrating that the supply of ammonia via glutamate dehydrogenase is the rate-limiting step in glutamine formation from glutamate. NH4Cl also inhibited the flux of glutamate through glutamate dehydrogenase and the formation of glucose, alanine and lactate. 6. The activities of enzymes possibly involved in the glutamate conversion into pyruvate were measured in guinea-pig renal cortex. 7. Renal arteriovenous-difference measurements revealed that in vivo the guinea-pig kidney adds glutamine and alanine to the circulating blood.

Aminooxyacetic Acid↗
PubMed1987

L-phenylalanyl-L-glutamate-stimulated, chloride-dependent glutamate binding represents glutamate sequestration mediated by an exchange system.

Stimulation of glutamate binding by the dipeptide L-phenylalanyl-L-glutamate (Phe-Glu) was inhibited by the peptidase inhibitor bestatin, suggesting that the stimulation was caused by glutamate liberated from the dipeptide and not by the dipeptide itself. It further suggests that this form of glutamate binding should be reinterpreted as glutamate sequestration and that stimulation of binding both by dipeptides and after preincubation with high concentrations of glutamate is likely to be due to counterflow accumulation. Several other criteria indicate that most of glutamate binding stimulated by chloride represents glutamate sequestration: Binding is reduced when the osmolarity of the incubation medium is increased, when membranes incubated with [3H]glutamate are lysed before filtration, and when membranes are made permeable by transient exposure to saponin. Moreover, dissociation of bound glutamate after a 100-fold dilution of the incubation medium is accelerated about 50 times by the addition of glutamate to the dilution medium. This result would be anomalous if glutamate were bound to a receptor site; it suggests instead that glutamate is transported in and out of membrane vesicles by a transport system that preferentially mediates exchange between internal and external glutamate. Glutamate binding contains a component of glutamate sequestration even when measured in the absence of chloride. Sequestration is adequately abolished only after treating membranes with detergents; even extensive lysis, sonication, and freezing/thawing may be insufficient.

Aminopeptidases↗
PubMed1999

Compromised glutamate transport in human glioma cells: reduction-mislocalization of sodium-dependent glutamate transporters and enhanced activity of cystine-glutamate exchange.

Elevated levels of extracellular glutamate ([Glu](o)) can induce seizures and cause excitotoxic neuronal cell death. This is normally prevented by astrocytic glutamate uptake. Neoplastic transformation of human astrocytes causes malignant gliomas, which are often associated with seizures and neuronal necrosis. Here, we show that Na(+)-dependent glutamate uptake in glioma cell lines derived from human tumors (STTG-1, D-54MG, D-65MG, U-373MG, U-251MG, U-138MG, and CH-235MG) is up to 100-fold lower than in astrocytes. Immunohistochemistry and subcellular fractionation show very low expression levels of the astrocytic glutamate transporter GLT-1 but normal expression levels of another glial glutamate transporter, GLAST. However, in glioma cells, essentially all GLAST protein was found in cell nuclei rather than the plasma membrane. Similarly, brain tissues from glioblastoma patients also display reduction of GLT-1 and mislocalization of GLAST. In glioma cell lines, over 50% of glutamate transport was Na(+)-independent and mediated by a cystine-glutamate exchanger (system x(c)(-)). Extracellular L-cystine dose-dependently induced glutamate release from glioma cells. Glutamate release was enhanced by extracellular glutamine and inhibited by (S)-4-carboxyphenylglycine, which blocked cystine-glutamate exchange. These data suggest that the unusual release of glutamate from glioma cells is caused by reduction-mislocalization of Na(+)-dependent glutamate transporters in conjunction with upregulation of cystine-glutamate exchange. The resulting glutamate release from glioma cells may contribute to tumor-associated necrosis and possibly to seizures in peritumoral brain tissue.

ATP-Binding Cassette Transporters↗
PubMed2002

Knocking out the glial glutamate transporter GLT-1 reduces glutamate uptake but does not affect hippocampal glutamate dynamics in early simulated ischaemia.

Glutamate release in ischaemia triggers neuronal death. The major glial glutamate transporter, GLT-1, might protect against glutamate-evoked death by removing extracellular glutamate, or contribute to death by reversing and releasing glutamate. Previous studies of the role of GLT-1 in ischaemia have often used the GLT-1 blocker dihydrokainate at concentrations that affect transporters other than GLT-1 and which affect kainate, N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In hippocampal slices from postnatal day 14 mice lacking GLT-1, the current response of area CA1 pyramidal cells to superfused AMPA and NMDA (which are not taken up) was unaffected, whereas the response to 100 microm glutamate was more than doubled relative to that in wild-type littermates, a finding consistent with a decrease in glutamate uptake. In response to a few minutes of simulated ischaemia, pyramidal cells in wild-type mice showed a large and sudden inward glutamate-evoked current [the anoxic depolarization (AD) current], which declined to a less inward plateau. In mice lacking GLT-1, the time to the occurrence of the AD current, its amplitude, the size of the subsequent plateau current and the block of the plateau current by glutamate receptor blockers were all indistinguishable from those in wild-type mice. We conclude that GLT-1 does not contribute significantly to glutamate release or glutamate removal from the extracellular space in early simulated ischaemia. These data are consistent with glutamate release being by reversal of neuronal transporters, and with uptake into glia being compromised by the ischaemia-evoked fall in the level of ATP needed to convert glutamate into glutamine.

2-Amino-5-phosphonovalerate↗
PubMed1984

[Effect of glutamic acid content of the diet on the catabolic rate of isotope-labeled glutamic acid in rats. 3. Determination of 14CO2 and 15N excretion following intragastric infusion of 14C- and 15N-glutamic acid].

Male rats (body weight 100 g) received during a 8 days experimental feeding period diets with different contents in glutamic acid. The daily feed intake was restricted to the energy maintenance level of 460 kJ/kg0.75. The diet contained a mixture of L-amino acids corresponding to the pattern of egg protein except glutamic acid. Glutamic acid was added successively at 10 levels (0 to 14,8% of dry matter) and the resulting diets were fed to groups of 4 animals each. At the end of the experimental feeding period 14C- and 15N-labelled glutamic acid were applied by intragastric infusion. CO2- and 14CO2-excretion was measured during the following 4 hours and the urinary N- and 15N-excretion during the following 24 hours. The CO2-excretion decreased from 53 to 44 mmol CO2/100 g body weight with increasing levels of dietary glutamic acid. This change seems to result from the increasing proportion of amino acids as an energetic fuel. While the amount of oxidized glutamic acid increased with increasing supplements of glutamic acid the relative 14CO2-excretion decreased from 57 to 48% of the applied radioactivity. The urinary 15N-excretion during 24 hours was 31% of the given amount of 15N if no glutamic acid was included in the diet. This proportion increased successively up to 52% in the case of the highest supply of glutamic acid. Because the total N-excretion increased at the same extent as the 15N-excretion a complete mixing of the NH2-groups resulting from glutamic acid due to desamination with the ammonia pool was assumed. No correlation between glutamic acid content of the diet and specific radioactivity of CO2 or atom-% 15N excess of urinary N was observed.

Animal Feed↗
PubMed1984

[Effect of glutamic acid content of the diet on the catabolic rate of isotope-labeled glutamic acid in rats. 2. Time course of 14CO2 excretion following subcutaneous administration of 14C-glutamic acid].

40 rats with a body weight of 100 g received 7 semisynthetic diets with different contents of glutamic acid and one diet contained whole egg. A L-amino acid mixture corresponding to the pattern of egg protein was the protein source of the semisynthetic diets. Glutamic acid was supplemented successively from 0 to 58 mol-% of the total amino acid content. On the 8th day of experimental feeding the animals were labelled by subcutaneous injection of 14C-U-L-glutamic acid. Subsequently the CO2- and the 14CO2-excretion were measured for 24 hours. In this period 64 to 68% of the injected radioactivity were recovered as 14CO2. The curve pattern of 14CO2-excretion indicates two different processes of 14CO2-formation. One characterizing the direct degradation of glutamic acid to CO2 with a high rate constant and a second one with a lower rate constant characterizing the 14CO2-formation via metabolites of glutamic acid. 77% of the total 14CO2-excretion in 24 hours resulted from the direct oxidation of glutamic acid and 23% from the oxidation of intermediates. When 14CO2-formation was measured 10 to 24 hours after injection of 14C-glutamic acid a positive correlation to the content of glutamic acid in the diet was observed. The intestinal tissue contribute considerably to the catabolization of glutamic acid, however, there seems to exist an upper limit for this capacity.

Animal Feed↗
PubMed1984

[Effect of glutamic acid content of the diet on isotope-labeled glutamic acid catabolism in rats. 1. The course of 14CO excretion following intragastric administration of 14C-glutamic acid].

Male rats received in 8 groups of 10 animals each for a period of 7 days 7 synthetic diets and one semisynthetic diet on maintenance requirement level. A L-amino acid mixture corresponding to the pattern of egg protein without glutamic acid was the protein source of the synthetic diets. Glutamic acid was supplemented successively from 0 to 58 mol-% of the total amino acid content. The crude protein source of diet 8 was whole egg powder. On the 8th day of experiment 5 animals per group were labelled by intragastric infusion (i.g.) with 14C-U-glutamic acid. During the following 24 hours the excretion of CO2 and 14CO2 was measured. Throughout the experimental feeding body weight was relative constant, however, when the synthetic diets were fed it was necessary to increase the daily amount of energy from 460 to 480 kJ/kg0,67. The relative 14CO2-excretion within 24 hours was 68-75% of the dose. However, the main part of the amount of radioactivity excreted during 24 hours was found after 4 to 6 hours already. Exponential functions calculated from the data of cumulative 14CO2-excretion suggest the existence of a fast process of 14CO2-formation directly from 14C-glutamic acid, reaching a plateau within 2 hours and a slow process of oxidation of intermediates of glutamic acid metabolism, causing a continued 14CO2-formation even after 24 hours. The oxidation of 14C-glutamic acid to CO2 decreased 2 to 14 hours after i.g. labelling if the glutamic acid content of the diet increased. The same was found for the specific radioactivity of 14CO2. A storage of intermediates of glutamic acid before degradation was assumed.

Animals↗
PubMed1985

Effects of anti-glutamate-binding protein antibodies on synaptic membrane ion flux, glutamate transport and release, and L-glutamate binding activities.

Antibodies (Abs) raised against the L-glutamate-binding protein (GBP) purified from bovine brain were used to define the possible physiologic activity of GBP in synaptic membranes. Three processes were examined for their sensitivity to the Abs: the excitatory amino acid stimulation of thiocyanate (SCN-) flux, the transport of L-glutamic acid across the synaptic membrane, and the depolarization-induced release of L-glutamate. Only the amino acid-induced changes in ion flux were inhibited by the anti-GBP Abs. The change in membrane potential produced by exposure of synaptic membranes to excitatory amino acids was measured as the increase in the uptake of the lipophilic anion SCN-. The L-glutamate-induced SCN- influx was 40 times more sensitive to inhibition by the anti-GBP Abs than the stimulation of ion flux by kainate, and 60 times more sensitive than that produced by quisqualate. The anti-GBP Abs did not inhibit the activation of ion flux produced by N-methyl-D-aspartate. The inhibition of glutamate-stimulated ion fluxes by the Abs was complete, whereas the inhibition of L-glutamate binding to either the rat or bovine brain GBP was not. The results obtained indicated that although the majority of the anti-GBP Abs were not directed against the glutamate recognition site of the GBP and of presumed synaptic membrane receptors, they were effective in blocking the activation of receptor-associated ion channels. Thus, the GBP may be considered a component of some excitatory amino acid receptor complexes.

Animals↗
PubMed1999

Role of glutamate receptors and glutamate transporters in the regulation of the glutamate-glutamine cycle in the awake rat.

In the present study we investigate the effects of a specific glutamate reuptake blocker, L-trans-pyrrolidine-3,4-dicarboxylic acid (PDC), on extracellular concentrations of glutamine and glutamate in the striatum of the freely moving rat. Intracerebral infusions of PDC (1, 2 and 4 mM) produced a dose-related increase in extracellular concentrations of glutamate and a dose-related decrease in extracellular concentrations of glutamine. These increases in extracellular glutamate and decreases in extracellular glutamine were significantly correlated. To investigate the involvement of ionotropic glutamate receptors in the decreases of extracellular glutamine produced by PDC, N-methyl-D-aspartate (NMDA) receptor antagonist and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor antagonist were used. Perfusion of the NMDA receptor antagonist blocked the decrease of extracellular glutamine but had no effect on the increase of extracellular glutamate, both produced by PDC. Perfusion of the AMPA/kainate receptor antagonist attenuated the increase of extracellular glutamate and not only blocked the decrease of extracellular glutamine but also produced a significant increase of extracellular glutamine. The results reported in this study suggest that both NMDA and AMPA/kainate glutamatergic receptors are involved in the regulation of extracellular glutamine.

ATP-Binding Cassette Transporters↗
PubMed1988

Kainic acid inhibits the synaptosomal plasma membrane glutamate carrier and allows glutamate leakage from the cytoplasm but does not affect glutamate exocytosis.

Kainate inhibits the exchange of D-aspartate into guinea-pig cerebrocortical synaptosomes. Kainate inhibits the Ca2+-independent efflux of endogenous glutamate in the presence of a trapping system for the released amino acid but potentiates a Ca2+-independent net efflux of endogenous and labelled glutamate and aspartate in the absence of the trap. Dihydrokainate has a similar effect. No discrepancy is seen between the release of endogenous and exogenously accumulated amino acid. These results are consistent with the presence of a slow leak of glutamate or aspartate from the cytoplasm independent of the kainate-sensitive Na+-cotransport pathway. In the presence of the trap, glutamate effluxes by both pathways, whereas in the absence of the trap, the Na+-cotransport pathway opposes the leak. Neither in the presence or absence of the glutamate trap does kainate induce, inhibit, or otherwise affect the Ca2+-dependent release of endogenous glutamate. The results enable many of the apparent complexities in the presynaptic actions of kainate to be resolved.

Amino Acid Transport System X-AG↗
PubMed1986

Induction of glutamate binding sites in hippocampal membranes by transient exposure to high concentrations of glutamate or glutamate analogs.

The number of Na+-independent, Cl--dependent glutamate binding sites in rat hippocampal membranes is increased two- to fourfold after pre-exposing isolated membranes or hippocampal slices to high concentrations (0.1-10 mM) of L-glutamate or of glutamate analogs with high affinity for this binding site, such as quisqualate, homocysteate, or aminoadipate. N-Methylaspartate and kainate are ineffective. A similar binding increase is induced by transient exposure to the dipeptide tyrosylglutamate. The newly induced binding sites appear to be identical with pre-existing Cl--dependent binding sites by several criteria: They have a similar pharmacological profile, they are sensitive to low concentrations of Na+, and the number of sites can be further increased by transient exposure to micromolar calcium concentrations. Moreover, binding of [3H]APB, a ligand selective for the Cl--dependent glutamate binding sites, is also increased after glutamate preincubation. The induction of binding sites by high glutamate concentrations, described herein, is calcium-independent, not inhibited by leupeptin and, therefore, different from the previously described activation of binding sites by a calcium-sensitive protease. The high concentration of ligand needed to induce increased binding suggests the presence in hippocampal membranes of a binding site with low, millimolar affinity that is functionally related to the known high-affinity binding sites. Several interpretations of the observed effects and their implications for the possible relationship between the binding site and the synaptic receptor are discussed.

2-Amino-5-phosphonovalerate↗
PubMed1985

[Effect of glutamic acid content in the diet on the catabolic rate of the isotope-labeled glutamic acid in rats. 4. Measurement of 14C-glutamic acid oxidation to 14CO2 with various energy sources in the diet].

48 male rats (body weight 80-100 g) were fed with 2 diets different in the glutamic acid content (diet I 2.42 and diet II 6.24% glutamic acid in the dry matter). The mixture of the other synthetic L-amino acids was adapted to the egg protein pattern corresponding 10% crude protein in the diet. Each diet was fed either on 73% or 98 to 104% of the energy maintenance requirement. After 7 days of experimental feeding 14C-U-L-glutamic acid was given to each group by intragastric infusion (i.g.), intraperitoneal (i.p.) or subcutaneous injection (s.c.), respectively, followed by a measurement of the CO2-and 14CO2-excretion during two subsequent periods of 3 hours. The CO2-excretion was lower in animals with restricted energy intake especially during the first 3 hour-period, which was started 2 hours after feed intake. The relative 14CO2-excretion (percent of the dose) was neither significantly influenced by the level of energy intake nor by the amount of dietary glutamic acid. The highest degradation rates of 14C-glutamic acid to 14CO2 were measured after i.g. application (more than 50%), followed by the i.p. injection (nearly 50%) and the lowest values were observed after s.c. injection (about 40%). These differences were only evident during the first CO2-absorption period. Furthermore the s.c. injection caused a lower specific radioactivity of CO2 compared with the data after i.g. and i.p. application. The results suggest the high metabolic activity of the intestinal tissue for glutamic acid.

Animal Feed↗
PubMed1983

Mechanism of glutamate transport in Escherichia coli B. 1. Proton-dependent and sodium ion dependent binding of glutamate to a glutamate carrier in the cytoplasmic membrane.

Specific binding of glutamate to its carrier was investigated by using cytoplasmic membrane vesicles prepared from Escherichia coli B. The binding activity was specifically affected by the Na+ and H+ concentrations of the medium. Cytoplasmic membrane vesicles from the mutant strain 36-39 that is defective in the Na+-dependent glutamate transport system showed no binding of glutamate. Addition of the protonophore uncoupler 3,5-di-tert-butyl-4-hydroxy-benzylidenemalononitrile or carbonyl cyanide m-chlorophenylhydrazone, or the ionophore monensin or nigericin, did not inhibit the binding, indicating that the binding reaction is not energy dependent. The parameters of binding were determined in reaction media with various combinations of H+ and Na+ concentrations. The maximum number of binding sites was constant and determined to be 70 pmol/mg of membrane protein, irrespective of the concentrations of H+ and Na+ in the medium. The apparent dissociation constant, however, was greatly affected by changes in the concentrations of both H+ and Na+, in such a way that it was expressed by a linear combination of the reciprocals of the H+ and Na+ concentrations. The characteristics of binding can be explained best by supposing that glutamate can bind only to a H+/Na+/carrier complex that is formed by random binding of H+ and Na+ to the unloaded carrier. The physiological role of this elementary binding reaction and of this quaternary complex as an active intermediate in the process of glutamate transport is discussed.

Biological Transport↗
PubMed1995

A NADP-glutamate dehydrogenase mutant of the petit-negative yeast Kluyveromyces lactis uses the glutamine synthetase-glutamate synthase pathway for glutamate biosynthesis.

The activities of the enzymes involved in ammonium assimilation and glutamate biosynthesis were determined in wild-type and NADP-glutamate dehydrogenase (GDH) null mutant strains of Kluyveromyces lactis. The specific NADP-GDH activity from K. lactis was fivefold lower than that found in Saccharomyces cerevisiae. The glutamine synthetase (GS) and glutamate synthase (GOGAT) activities were similar to those reported in S. cerevisiae. The NADP-GDH null mutant was obtained by transforming the uraA strain MD2/1 with a linearized integrative yeast vector harbouring a 390 bp fragment of the NADP-GDH structural gene. This mutant grew as well as the parent strain on ammonium, but showed GS and GOGAT activities higher that those found in the wild-type strain, implying that the GS-GOGAT pathway could play a leading role in glutamate biosynthesis in K. lactis. Southern blotting analysis of K. lactis chromosomes separated by contour-clamped homogeneous electric field electrophoresis, indicated that the NADP-GDH structural gene is localized on chromosome VI.

Amino Acid Sequence↗
PubMed1994

Flow injection determination of glutamate in human serum and rat brain samples with immobilized glutamate oxidase and glutamate dehydrogenase reactors.

Two methods are proposed for the determination of regional concentrations of glutamate in the rat brain as well as in human serum. Glutamate oxidase was immobilized on non-porous glass beads and glutamate dehydrogenase was immobilized on glass derivatives. These supports were employed for the construction of Single Bead String Reactors and Packed Bed Reactors, respectively, which in turn were linked to Flow Injection Analysis systems with either photometric or fluorometric detection. Analytical working curves are linear in the range 1-200 mumol/l for packed bed reactors and 10-500 mmol/l for single bead string reactors. The samples were pretreated depending on their origin and the applied measuring system. Optimal dilution factors were established for the two techniques. Optimal dilution ratios were established and the influence of several added substances was investigated. Recovery and method comparison studies including high performance liquid chromatography verified the accuracy of the proposed methods. Results from within-day and between-day measurements gave relative standard deviations of 4.7 and 5.9% for serum samples and 2.5 and 4.0% for brain samples, respectively.

Amino Acid Oxidoreductases↗
PubMed2001

The role of the active site glutamate in the rearrangement of glutamate to 3-methylaspartate catalyzed by adenosylcobalamin-dependent glutamate mutase.

BACKGROUND: Adenosylcobalamin (coenzyme B(12))-dependent enzymes catalyze a variety of chemically difficult reactions that proceed through the generation of free radical intermediates. A long-standing question is how proteins stabilize what are normally regarded as highly reactive organic radicals and direct them towards productive reactions. In glutamate mutase the carboxylate of Glu171 hydrogen bonds with the amino group of the substrate. We have investigated the role of this residue in the enzyme mechanism. RESULTS: Several sterically and functionally conservative mutations were introduced at position 171. In the most impaired mutant, Glu171Gln, k(cat) is reduced 50-fold, although the K(m) for glutamate is little affected. In the wild-type enzyme activity was pH-dependent and the acidic limb of the activity curve titrated with an apparent pK(a) of 6.6 on V(max), whereas for the sluggish Glu171Gln mutant activity is independent of pH. The steady state deuterium kinetic isotope effect is reduced in the mutant enzyme, but the steady state concentration of free radical species on the enzyme (as measured by the steady state concentration of cob(II)alamin) is unaffected by the mutation. CONCLUSIONS: The properties of the mutant proteins are consistent with the hypothesis that Glu171 acts as a general base that serves to deprotonate the amino group of the substrate during catalysis. Deprotonation is expected to facilitate the formation of the glycyl radical intermediate formed during the inter-conversion of substrate and product radicals, but to have little effect on the stability of product or substrate radicals themselves.

Aspartic Acid↗
PubMed1983

Cerebral glutamate, neuroleptic drugs and schizophrenia: increase of cerebrospinal fluid glutamate levels and decrease of striate body glutamate levels following sulpiride treatment in rats.

Chronic (12 days) administration of sulpiride (50 mg/kg, i.p.) in rats resulted in a significant (12%) increase in the glutamate contents of cerebrospinal fluid. Sulpiride had no effect on the GABA content of the brain areas investigated (frontal cortex, striatum, hippocampus and substantia nigra). Sulpiride is a neuroleptic drug which is believed to block especially the non-adenylate cyclase dopaminergic receptors which are supposed to be inhibitory axoaxonic receptors on glutamatergic corticostriatal terminals. The results are compatible with the hypothesis that glutamatergic hypofunction might be the primary defect in schizophrenia rather than hyperactivity of the dopamine synapses.

Animals↗
PubMedDate not supplied

Astroglia and glutamate in physiology and pathology: aspects on glutamate transport, glutamate-induced cell swelling and gap-junction communication.

Astroglia have the capacity to monitor extracellular glutamate (Glu) and maintain it at low levels, metabolize Glu, or release it back into the extracellular space. Glu can induce an increase in astroglial cell volume with a resulting decrease of the extracellular space, and thereby alter the concentration of extracellular substances. Many lines of evidence show that K(+) can be buffered within the astroglial gap-junction-coupled network, and recent results show that gap junctions are permeable for Glu. All these events occur dynamically: the astroglial network has the capacity to interfere actively with neurotransmission, thereby contributing to a high signal-to-noise ratio for the Glu transmission. High-quality neuronal messages during normal physiology can then be maintained. With the same mechanisms, astroglia might exert a neuroprotective function in situations of moderately increased extracellular Glu concentrations, i.e., corresponding to conditions of pathological hyper-excitability, or corresponding to early stages of an acute brain injury. If the astroglial functions are failing, neuronal dysfunction can be reinforced.

Animals↗