Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “GLUTAMATES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources
PubMed2006

Overexpression in Arabidopsis of a plasma membrane-targeting glutamate receptor from small radish increases glutamate-mediated Ca2+ influx and delays fungal infection.

Ionotropic glutamate receptors (iGluRs) are ligand-gated nonselective cation channels that mediate fast excitatory neurotransmission. Although homologues of the iGluRs have been identified in higher plants, their roles are largely unknown. In this work we isolated a full-length cDNA clone (RsGluR) encoding a putative glutamate receptor from small radish. An RsGluR: mGFP fusion protein was localized to the plasma membrane. In Arabidopsis thaliana overexpressing the full-length cDNA, glutamate treatment triggered greater Ca2+ influx in the root cells of transgenic seedlings than in those of the wild type. Transgenic plants exhibited multiple morphological changes such as necrosis at their tips and the margins of developing leaves, dwarf stature with multiple secondary inflorescences, and retarded growth, as previously observed in transgenic Arabidopsis overexpressing AtGluR3.2 [Kim et al. (2001)]. Microarray analysis showed that jasmonic acid (JA)-responsive genes including defensins and JA-biosynthetic genes were up-regulated. RsGluR overexpression also inhibited growth of a necrotic fungal pathogen Botrytis cinerea possibly due to up-regulation of the defensins. Based on these results, we suggest that RsGluR is a glutamate-gated Ca2+ channel located in the plasma membrane of higher plants and plays a direct or indirect role in defense against pathogen infection by triggering JA biosynthesis.

Amino Acid Sequence↗
PubMed1996

Calmodulin binding to glutamate decarboxylase is required for regulation of glutamate and GABA metabolism and normal development in plants.

Glutamate decarboxylase (GAD) catalyzes the decarboxylation of glutamate to CO2 and gamma-aminobutyrate (GABA). GAD is ubiquitous in prokaryotes and eukaryotes, but only plant GAD has been shown to bind calmodulin (CaM). Here, we assess the role of the GAD CaM-binding domain in vivo. Transgenic tobacco plants expressing a mutant petunia GAD lacking the CaM-binding domain (GADdeltaC plants) exhibit severe morphological abnormalities, such as short stems, in which cortex parenchyma cells fail to elongate, associated with extremely high GABA and low glutamate levels. The morphology of transgenic plants expressing the full-length GAD (GAD plants) is indistinguishable from that of wild-type (WT) plants. In WT and GAD plant extracts, GAD activity is inhibited by EGTA and by the CaM antagonist trifluoperazine, and is associated with a CaM-containing protein complex of approximately 500 kDa. In contrast, GADdeltaC plants lack normal GAD complexes, and GAD activity in their extracts is not affected by EGTA and trifluoperazine. We conclude that CaM binding to GAD is essential for the regulation of GABA and glutamate metabolism, and that regulation of GAD activity is necessary for normal plant development. This study is the first to demonstrate an in vivo function for CaM binding to a target protein in plants.

Calmodulin↗
PubMed1994

Potentiation of synaptic transmission in the rat hippocampal slice by exogenous L-glutamate and selective L-glutamate receptor subtype agonists.

We have investigated the effects of administration of exogenous glutamate receptor agonists on the amplitude of field excitatory post-synaptic potentials (fEPSPs) evoked in the CA1 region of the rat hippocampal slice by stimulation of the Schaffer collateral-commissural fibres. L-Glutamate applied by iontophoresis or by bath perfusion (50 microM for 5 min) evoked a slowly rising increase in the amplitude of the fESPS which persisted for over 90 min. L-Glutamate induced potentiation was blocked by either D(-)-2-amino-5-phosphonopentanoic acid (40 microM) or by (RS)-alpha-methyl-4-carboxyphenylglycine (500 microM). In slices in which synaptic long-term potentiation had been saturated, iontophoretically applied L-glutamate did not induce further potentiation, but reset the fEPSP amplitude back to control levels. Iontophoretic administration of N-methyl-D-aspartate (NMDA) evoked a transient potentiation which decayed back to control levels within 90 min whereas bath perfusion of NMDA (50 microM) evoked a persistent depression. Bath perfusion of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, 50 microM) evoked no persistent effects. Bath administration of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD, 50 or 100 microM) caused a short term depression of the fEPSP and no significant persistent effects. Perfusion of 100 microM ACPD in medium containing 1 microM picrotoxin caused a much smaller short term depression of the fEPSP and this was followed by a gradually developing and persistent potentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Postnatal changes in the activity of glutamate dehydrogenase and aspartate aminotransferase in the rat nervous system with special reference to the glutamate transmitter metabolism.

The activities of aspartate aminotransferase (AAT) and glutamate dehydrogenase (GIDH), the major glutamate metabolizing enzymes, were studied in hippocampal formation, cerebellar cortex, dorsal root ganglia, superior cervical ganglia and liver as a function of postnatal development. At birth, in all these nervous tissues the enzyme activities were quite low and showed similar levels (AAT 7-15 U/g wet weight; 0.18-0.23 U/mg protein; GIDH 3.4-13 U/g wet weight; 0.07-0.18 U/mg protein). Based on protein, AAT activity increased during the postnatal period studied 5.8 and 3.8 times in the hippocampal formation and cerebellar cortex, respectively, while the respective GIDH rise was 5.2 and 2.3 times. During postnatal maturation, enzyme activities in dorsal root ganglia showed only minor changes. In superior cervical ganglia, AAT and GIDH were remarkably constant. In liver the enzyme activities changed during postnatal development, but the activity curve profile was quite distinct from those obtained for brain regions. The steep rise of AAT and GIDH activities in brain regions is discussed as being a consequence of the maturation of preferably glutamatergic structures. Glutamatergic transmission processes obviously do not take place in superior cervical ganglia and dorsal root ganglia, and certainly not in liver. The present results suggest a quantitatively significant participation of glutamate transmitter metabolism in proportion to the whole glutamate metabolism of the CNS.

Aging↗
PubMed1996

The effect of chronic haloperidol treatment on glutamate receptor subunit (GluR1, GluR2, KA1, KA2, NR1) mRNAs and glutamate binding protein mRNA in rat forebrain.

Antipsychotic (neuroleptic) drugs have effects on the glutamatergic system which include changes in the expression of glutamate receptor subunits. There are, however, no long-term studies. We have investigated the influence of 16 weeks' treatment with haloperidol on eight glutamate receptor mRNAs in dorsolateral striatum, frontoparietal cortex and hippocampus using in situ hybridization histochemistry. The mRNAs targetted were the flip and flop isoforms of GluR1 and GluR2, KA1 and KA2, NR1, and the glutamate binding protein (GBP). The flip isoform of GluR2 was elevated in striatum and cortex, leading to an increase in the GluR2 flip/flop ratio. KA2 mRNA was increased in hippocampus and cortex. GBP mRNA was increased in striatum. The other mRNAs were unaffected. The data show that the profile of glutamate receptor subunit mRNA expression is altered in a molecularly and anatomically selective way following chronic haloperidol administration. They provide another indication of glutamatergic involvement in the biochemical response to antipsychotic medication.

Animals↗
PubMed1977

Identification of glutamate chain lengths of endogenous folylpoly-gamma-glutamates in rat tissues.

A simplified procedure for the determination of the glutamate chain lengths of endogenous tissue folate is described. Natural pteroylpoly-gamma-glutamates in tissue extracts, irrespective of their one-carbon moiety, were converted by a reductive cleavage procedure to a homologous series of p-aminobenzoylpoly-gamma-glutamates, differing only in glutamate chain length. Desalting and concentration of the extracts were achieved by absorbing the derivatives on active charcoal followed by their elution with ethanol:ammonia. Aminobenzoylpolyglutamates were separated by DEAD-cellulose chromatography and quantitated by a colorimetric procedure for primary aromatic amines. The major endogenous folates in rat liver and kidney were pteroylpentaglutamate derivatives with smaller amounts of pteroyltetra- and hexaglutamate.

Animals↗
PubMed1991

Functional studies of a glutamate dehydrogenase with known three-dimensional structure: steady-state kinetics of the forward and reverse reactions catalysed by the NAD(+)-dependent glutamate dehydrogenase of Clostridium symbiosum.

Steady-state kinetic properties of glutamate dehydrogenase from Clostridium symbiosum are reported. Rates with NADP(H) are over three hundred times lower than with NAD(H) under identical conditions. The 3-acetyl pyridine and 6-deamino adenine analogues of NAD+, on the other hand, are used almost as well as NAD+ itself. Amino acid specificity is very tight at both pH 7 and pH 9. The best alternative substrate of those tested, L-alpha-amino-gamma-nitraminobutyrate, gave only 0.5% of the rate seen with glutamate. With 400 microM NAD+ a 160-fold variation of the glutamate concentration gave a linear Eadie plot apart from slight inhibition at the highest concentrations. With 40 mM L-glutamate and varied [NAD+], the Eadie plot appeared linear between 1.6 microM and 60 microM and again between 60 microM and 2000 microM, but the slopes of the two lines differed by a factor of 8.4. This striking pattern is not attributable to impurities in the coenzyme or to changes in the state of aggregation of the enzyme. For the high concentration range (greater than 60 microM NAD+), the presence of all four linear terms in the reciprocal form of the initial rate equation indicates a sequential mechanism. Similar measurements made for APAD+ and dnNAD+ show no sign of non-linearity in the Eadie plot over the wide concentration ranges explored. In the reductive amination direction, with NADH as coenzyme, linear reciprocal plots were obtained for all three substrates. Systematic variation of concentrations led via primary, secondary and tertiary plots to all eight possible initial-rate parameters in a linear reciprocal initial-rate equation. Compulsory-order and enzyme-substitution mechanisms appear to be excluded, and a random route to the central complex seems the only possibility compatible with the results.

Amines↗
PubMed1983

The corticopontine projection: axotomy-induced loss of high affinity L-glutamate and D-aspartate uptake, but not of gamma-aminobutyrate uptake, glutamate decarboxylase or choline acetyltransferase, in the pontine nuclei.

The corticopontine fibres were severed in the crus cerebri in rats and mice by a stereotaxically operated retractable wire-knife. The pontine nuclei were microscopically dissected from fresh slices of rats and synaptosome-containing homogenates were prepared. The high affinity uptake of radiolabelled L-glutamate (L-Glu) and D-aspartate (D-Asp) was heavily reduced five days after the lesions. The uptake was further reduced after bilateral (-75% for D-Asp and -65% for L-Glu) than after unilateral lesions (-55% for D-Asp and -45 to 50% for L-Glu on the lesioned side.) The molar ratio of the uptakes of D-Asp and L-Glu was consistently lower in pons after transection of the cortical afferents than normally (-28% after bilateral lesions). gamma-Aminobutyrate uptake and glutamic acid decarboxylase were not changed. Choline acetyltransferase was increased (+53%) after unilateral lesions, but not altered after bilateral lesions. Autoradiograms of slices from mice, incubated with tritium-labelled amino acids and fixed in glutaraldehyde, showed high affinity uptake sites for D-Asp to be enriched in the pontine nuclei, compared to neighbouring structures. After partial lesion of the crus cerebri the uptake was reduced in the area with degenerated corticopontine afferents. gamma-Aminobutyrate uptake sites were relatively less concentrated in the pontine nuclei than D-Asp uptake sites. The results indicate, along with the previous demonstration of Ca-dependent K-induced release of D-[3H]aspartate from the corticopontine terminals, that glutamate and/or aspartate may be transmitters in this pathway. The results also suggest that acidic amino acid uptake sites may differ in their relative transport rates for aspartate and glutamate.

Animals↗
PubMed1992

A possible role for nitric oxide in glutamate (MSG)-induced Chinese restaurant syndrome, glutamate-induced asthma, 'hot-dog headache', pugilistic Alzheimer's disease, and other disorders.

Endogenous glutamate is thought to be a major neurotransmitter. After binding to a cell membrane receptor there can be a stimulation of what can be called the nitric oxide (NO)-mediated neurotransmission pathway (NO-MNP). The activity of the enzyme that produces NO from arginine, NO synthase, and the level of NO become elevated. NO has little activity within the cell in which it is produced, but it rapidly leaks out of that cell and produces effects in neighboring cells. The NO-MNP can be activated to release NO in endothelial cells which in turn acts on neighboring vascular smooth muscle cells to induce vasodilation. Therefore, we suggest that exogenous, ingested glutamate, like endogenous glutamate, can lead to the same stimulation of the NO-MNP in sensitive individuals which would then cause the symptoms of the Chinese restaurant syndrome and/or glutamate-induced asthma. Further, since ingested nitrite and related compounds can be metabolized to NO, NO may more directly cause the symptoms of 'hot dog headache'. In addition, it has been suggested that NO production can also be controlled in endothelial cells by fluid forces that stimulate pressure receptors. Therefore, elevations of NO and stimulation of the NO-MNP may occur due to sudden, local, alterations of blood pressure during pugilistic activities and play a role in the symptoms of pugilistic Alzheimer's disease. If these ideas are correct, then inhibitors of the NO-MNP and/or temporary reduction of the plasma level of arginine may be useful in preventing at least some of the symptoms of these disorders.

Alzheimer Disease↗
PubMed2006

Mapping active site residues in glutamate-5-kinase. The substrate glutamate and the feed-back inhibitor proline bind at overlapping sites.

Glutamate-5-kinase (G5K) catalyzes the controlling first step of proline biosynthesis. Substrate binding, catalysis and feed-back inhibition by proline are functions of the N-terminal approximately 260-residue domain of G5K. We study here the impact on these functions of 14 site-directed mutations affecting 9 residues of Escherichia coli G5K, chosen on the basis of the structure of the bisubstrate complex of the homologous enzyme acetylglutamate kinase (NAGK). The results support the predicted roles of K10, K217 and T169 in catalysis and ATP binding and of D150 in orienting the catalytic lysines. They support the implication of D148 and D150 in glutamate binding and of D148 and N149 in proline binding. Proline increases the S(0.5) for glutamate and appears to bind at a site overlapping with the site for glutamate. We conclude that G5K and NAGK closely resemble each other concerning substrate binding and catalysis, but that they have different mechanisms of feed-back control.

Adenosine Triphosphate↗
PubMed2006

Methotrexate induces seizure and decreases glutamate uptake in brain slices: prevention by ionotropic glutamate receptors antagonists and adenosine.

Methotrexate (MTX)-induced neurotoxicity may occur after intrathecal or systemic administration at low, intermediate and high doses for the treatment of malignant or inflammatory diseases. The mechanisms of MTX neurotoxicity are not totally understood, and appear to be multifactorial. In this study we characterized a model of MTX-induced seizures in mice to evaluate the convulsive and toxic MTX properties. Additionally, the effect of MTX-induced seizures on the activity of glutamate transporters, as well as the anticonvulsant role of MK-801, DNQX and adenosine on glutamate uptake in brain slices was investigated . MTX induced tonic-clonic seizures in approximately 95% of animals and pre-treatment with MK-801, DNQX and adenosine prevented seizure in 80%, 62% and 50% of animals, respectively. Moreover, MTX leads 59% of mice to death, which was prevented in 100% and 94% when animals received MK-801 and DNQX, respectively. Glutamate uptake decreased by 20% to 30% in cortical slices after MTX-induced seizures. Interestingly, when seizures were prevented by MK-801, DNQX or adenosine, glutamate uptake activity remained at the same level as the control group. Thus, our results demonstrate the involvement of the glutamatergic system in MTX-induced seizures.

Adenosine↗
PubMed2006

Changes in glial glutamate transporters in human epileptogenic hippocampus: inadequate explanation for high extracellular glutamate during seizures.

Temporal lobe epilepsy (TLE) with hippocampal sclerosis is associated with high extracellular glutamate levels, which could trigger seizures. Down-regulation of glial glutamate transporters GLAST (EAAT1) and GLT-1 (EAAT2) in sclerotic hippocampi may account for such increases. Their distribution was compared immunohistochemically in non-sclerotic and sclerotic hippocampi and localized only in astrocytes, with weaker immunoreactivity for both transporters in areas associated with pronounced neuronal loss, especially in CA1, but no decrease or even an increase in areas with less neuronal loss, like CA2 and the subiculum in the sclerotic group. Such compensatory changes in immunoreactivity may account for the lack of differences between the groups in immunoblot studies as blots show the average concentrations in the samples. These data suggest that differences in glial glutamate transporter distribution between the two groups of hippocampi may be an insufficient explanation for the high levels of extracellular glutamate in sclerotic seizure foci observed through in vivo dialysis studies.

Adolescent↗
PubMed1996

Glutamate 94 of [2Fe-2S]-ferredoxins is important for efficient electron transfer in the 1:1 complex formed with ferredoxin-glutamate synthase (GltS) from Synechocystis sp. PCC 6803.

We have analyzed the role of critical amino acid residues involved in the interaction between ferredoxin and ferredoxin-glutamate synthase (GOGAT) encoded by the gltS gene from the cyanobacterium Synechocystis sp. PCC 6803. Our results indicated that the glutamate 94 residue of Anabaena 7120 ferredoxin (= E92 of the Synechocystis 6803 ferredoxin) was necessary for an efficient electron transfer to GOGAT comparable to ferredoxin:NADP-reductase, nitrite reductase and nitrate reductase [Schmitz and Böhme (1995) Biochim. Biophys. Acta 1231, 335-341]. The K(m) value determined for wt-ferredoxins and mutant E94Q (and E92Q) was 1 muM, respectively, and activity loss of E94Q was due to a lowered Vmax. Exchange of residue F65 for aliphatic substitutions, which was crucial to electron transfer to ferredoxin:NADP-reductase and nitrite reductase, exhibited only small effects on glutamate synthase-dependent activity while heterocyst ferredoxin and flavodoxin were almost inactive as electron donors. In contrast to data reported for the spinach system, the stoichiometry of the cross-linked complex between ferredoxin and glutamate synthase was 1:1.

Amino Acid Oxidoreductases↗
PubMed2002

A glutamate-gated chloride channel subunit from Haemonchus contortus: expression in a mammalian cell line, ligand binding, and modulation of anthelmintic binding by glutamate.

Glutamate-gated chloride channels (GluCls) are inhibitory ion channels that are sensitive to the antiparasitic drugs ivermectin (IVM) and moxidectin (MOX). We have transiently transfected COS-7 cells with a subunit of a GluCl (HcGluCla) from the parasitic nematode Haemonchus contortus. This subunit bound [3H]-IVM and [3H]-MOX with K(d) values of 0.11+/-0.021 and 0.18+/-0.02nM, respectively. Displacement analysis revealed that IVM and MOX bind to the same site on HcGluCla and that this site is likely distinct from the glutamate binding site. Glutamate was found to be an allosteric modulator of [3H]-MOX and [3H]-IVM binding and increased the affinity of [3H]-MOX for HcGluCla by more than 50% and that of [3H]-IVM by more than 7-fold. These results point to both similarities and differences in the interactions of IVM and MOX with the GluCl. Aspartate, which is structurally similar to glutamate, had little or no effect on [3H]-IVM and [3H]-MOX binding, suggesting that this ligand does not induce the conformational change necessary to potentiate macrocyclic lactone binding. These results also indicate that it may be possible to enhance the efficacy of macrocyclic lactone anthelmintics by administering these compounds with ligands acting allosterically to enhance their binding.

Animals↗
PubMed2000

Quantitative evaluation of extracellular glutamate concentration in postischemic glutamate re-uptake, dependent on brain temperature, in the rat following severe global brain ischemia.

Changes in brain temperature are known to modulate the marked neuronal damage caused by an approximately 10-min intra-ischemic period. Numerous studies have suggested that the extracellular glutamate concentration ([Glu](e)) in the intra-ischemic period and the initial postischemia period is strongly implicated in such damage. In this study, the effects of intra-ischemic brain temperature (32, 37, 39 degrees C) on [Glu](e) were investigated utilizing a dialysis electrode combined with ferrocene bovine serum albumin (BSA), which allows oxygen-independent real-time measurement of [Glu](e). This system allowed separate quantitative evaluation of intra-ischemic biphasic glutamate release from the neurotransmitter and metabolic pools, and of postischemic glutamate re-uptake in ischemia-reperfusion models. The biphasic [Glu](e) elevation in the intra-ischemic period did not differ markedly among intra-ischemic brain temperatures ranging from 32 to 39 degrees C. Intra-ischemic normothermia (37 degrees C) and mild hyperthermia (39 degrees C) markedly inhibited [Glu](e) re-uptake during the postischemic period, although the intra-ischemic [Glu](e) elevation did not differ from that during intra-ischemic hypothermia (32 degrees C). It was assumed that normothermia or mild hyperthermia in the intra-ischemic period influences intracellular functional abnormalities other than the intra-ischemic [Glu](e) elevation, thereby inhibiting glutamate re-uptake after reperfusion rather than directly modulating intra-ischemic [Glu](e) dynamics.

Animals↗
PubMed1998

Inducible expression of the GLT-1 glutamate transporter in a CHO cell line selected for low endogenous glutamate uptake.

Inducible expression of the mammalian glial cell glutamate transporter GLT-1 has been established in a CHO cell line selected for low endogenous Na+-dependent glutamate uptake by [3H]aspartate suicide selection. Culturing the cells in doxycycline-containing medium, to activate GLT-1 expression via the Tet-On system, increased uptake of the GLT-1 substrate D-aspartate 280-fold, and increased cell size. Applying glutamate to whole-cell clamped, doxycycline-treated cells evoked a transporter-mediated current with characteristics appropriate for GLT-1. This cell line provides a useful tool for further examination of the electrical, biochemical and pharmacological properties of GLT-1, the most abundant glutamate transporter in the brain.

ATP-Binding Cassette Transporters↗
PubMed2003

A microdialysis study of glutamate concentration in the hippocampus of rats after TsTX toxin injection and blockade of toxin effects by glutamate receptor antagonists.

Scorpion toxins act on ionic channels changing the release of neurotransmitters. In the present study, we investigated the glutamatergic release evoked by intrahippocampal injection of TsTX toxin isolated from Tityus serrulatus scorpion venom in male Wistar rats and the blockade of the toxin effect by glutamatergic antagonists. Microdialysis for neurotransmitter level quantification, electroencephalographic recording, and histopathological analysis were performed. The microdialysis method revealed enhanced levels of extracellular glutamate in the hippocampal area. The toxin injection preceded by injection of the glutamate receptor antagonists dizolcipine maleate (MK-801), D(-)2-amino-5-phosphonopentanoic acid (AP-5), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), L(+)-2-amino-3-phosphonopropionic acid (AP-3), and (+)-alpha-methyl-4-carboxyphenylglycine (MCPG) demonstrated that MK-801 and AP-5 fully blocked the electrographic alterations and the CA1 cell loss induced by the toxin. CNQX, AP-3, and MCPG partially blocked the epileptiform discharges and no hippocampal damage was observed. Thus, we conclude that the toxin evokes glutamate release and that glutamate receptor antagonists can partially or totally block the toxin effect.

Amino Acids↗
PubMed1997

Extrasynaptic glutamate spillover in the hippocampus: dependence on temperature and the role of active glutamate uptake.

At excitatory synapses on CA1 pyramidal cells of the hippocampus, a larger quantal content is sensed by N-methyl-D-aspartic acid receptors (NMDARs) than by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). A novel explanation for this discrepancy is that glutamate released from terminals presynaptic to one cell can diffuse to and activate NMDARs, but not AMPARs, on a neighboring cell. If this occurs in the living brain, it could invalidate the view that glutamatergic synapses function as private communication channels between neurons. Here, we show that the discrepancy in quantal content mediated by the two receptors is greatly decreased at physiological temperature, compared with conventional recording conditions. This effect of temperature is not due to changes in release probability or uncovering of latent AMPARs. It is, however, partially reversed by the glutamate uptake inhibitor dihydrokainate. The results suggest that glutamate transporters play a critical role in limiting the extrasynaptic diffusion of glutamate, thereby minimizing cross-talk between neighboring excitatory synapses.

Animals↗