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 343 records · Page 19Linked to original sources
PubMed1999

The Aspergillus nidulans gltA gene encoding glutamate synthase is required for ammonium assimilation in the absence of NADP-glutamate dehydrogenase.

Mutants of Aspergillus nidulans lacking NADP-glutamate dehydrogenase activity grow more poorly than wild-type strains on ammonium as a sole nitrogen source. The leaky growth of these mutants is indicative of an alternative pathway of ammonium assimilation and glutamate biosynthesis. We have PCR-amplified a portion of the A. nidulans gene encoding glutamate synthase and used this sequence to inactivate the genomic copy. This gene, designated gltA, was found to be dispensable for growth on ammonium in the presence of NADP-glutamate dehydrogenase activity. However, a strain carrying the gltA inactivation together with an NADP-glutamate dehydrogenase structural gene mutation (gdhA) was unable to grow on ammonium or on nitrogen sources metabolized via ammonium. The gltA gene was located to linkage group V of the A. nidulans genetic map.

Amino Acid Sequence↗
PubMed1999

High protein diet induces pericentral glutamate dehydrogenase and ornithine aminotransferase to provide sufficient glutamate for pericentral detoxification of ammonia in rat liver lobules.

The liver plays a central role in nitrogen metabolism. Nitrogen enters the liver as free ammonia and as amino acids of which glutamine and alanine are the most important precursors. Detoxification of ammonia to urea involves deamination and transamination. By applying quantitative in situ hybridization, we found that mRNA levels of the enzymes involved are mainly expressed in periportal zones of liver lobules. Free ammonia, that is not converted periportally, is efficiently detoxified in the small rim of hepatocytes around the central veins by glutamine synthetase preventing it from entering the systemic circulation. Detoxification of ammonia by glutamine synthetase may be limited due to a shortage of glutamate when the nitrogen load is high. Adaptations in metabolism that prevent release of toxic ammonia from the liver were studied in rats that were fed diets with different amounts of protein, thereby varying the nitrogen load of the liver. We observed that mRNA levels of periportal deaminating and transaminating enzymes increased with the protein content in the diet. Similarly, mRNA levels of pericentral glutamate dehydrogenase and ornithine aminotransferase, the main producers of glutamate in this zone, and pericentral glutamine synthetase all increased with increasing protein levels in the diet. On the basis of these changes in mRNA levels, we conclude that: (a) glutamate is produced pericentrally in sufficient amounts to allow ammonia detoxification by glutamine synthetase and (b) in addition to the catalytic role of ornithine in the periportally localized ornithine cycle, pericentral ornithine degradation provides glutamate for ammonia detoxification.

Ammonia↗
PubMed2005

Effect of chronic glutamate administration to pregnant rats during gestation on metabotropic glutamate receptors from mothers and full-term fetuses brain.

Chronic glutamate treatment during gestational period caused a significant decrease in total metabotropic glutamate receptors (mGluR) number. Similar results were observed on the steady-state level of mGlu(1) receptor detected by immunoblotting assays, suggesting that this is the main receptor subtype modulated by agonist exposure. Furthermore, no variations on mRNA coding mGlu(1) receptor were found, suggesting post-transcriptional modulation as a possible mechanism of the lost of receptor detected at the membrane surface. On the other hand, western-blotting to determine level of G(q/11) protein and phospholipase C beta(1) revealed a significant decrease of both proteins in mothers brain. This decrease was associated with significant variation in glutamate and DHPG-stimulated phospholipase C activity. No significant differences on mGluR transduction pathway components were observed in fetuses brain. These results suggest that glutamate intake during pregnancy causes a down-regulation of different proteins involved in glutamate response mediated by mGluR only in mothers brain without significantly affecting fetuses brain.

Administration, Oral↗
PubMed1985

Ornithine as a precursor of neurotransmitter glutamate: effect of canaline on ornithine aminotransferase activity and glutamate content in the septum of rat brain.

Local injections of L-canaline into the septum produce a rapid and almost complete inhibition of ornithine aminotransferase activity followed by a decrease in glutamate content in this region. The time-course of canaline action shows the existence of two glutamate pools with different sizes and half-life values. Surgical lesions of the hippocampal-septal glutamatergic pathway affected the site and kinetics of the small pool of glutamate in the septum, suggesting the participation of ornithine aminotransferase in the synthesis of this pool. This indicates a possible role of ornithine as a precursor of the transmitter glutamate. The localization of ornithine aminotransferase does not seem, however, to be specific for the nerve-terminal compartment. The data obtained allow estimation of the turnover rate of the specific pool of neurotransmitter glutamate.

Aminobutyrates↗
PubMed1993

Study of the stereoselectivity of L-glutamate receptors by synthetic 4(R)- and 4(S)-substituted L-glutamate analogues.

R- and S-stereoisomers of 4-substituted L-glutamate analogues are used to study the stereoselectivity of L-glutamate receptors. It is found that 4(R)-substituted analogues are more potent than their 4(S)-isomers in interacting with L-glutamate receptors both at porcine brain synaptic junctions and on drosophila muscles. This demonstrates that the ligand recognition site of L-glutamate receptors has chiral selectivity discriminating L-glutamate analogues with bulky 4(R)- and 4(S)-substituent groups.

Animals↗
PubMed1975

Effects of glutamate and glutamic acid diethyl ester on the lobster muscle fibre and the frog spinal cord.

The effect of bath applications of glutamic acid diethyl ester (GDE) and glutamate on the lobster muscle fibre and the from spinal cord were examined. In the lobster muscle fibre GDE (2 X 10(-3) M) did not antagonize the depolarizing action of glutamate (10(-4) M). In the frog spinal cord a small reduction in the excitatory effects of glutamate (10(-4)-10(-3) M) after GDE pretreatment was found only if the latter was given in very high doses (over 2 X 10(-3) M) which stimulated the neuronal firing. These observations show that GDE is not a specific antagonist of glutamate in these tissues.

Action Potentials↗
PubMed1989

Cytochalasin D inhibits L-glutamate-induced disc shedding without altering L-glutamate-induced increase in adhesiveness.

Excitatory amino acid-stimulated disc shedding is correlated with the appearance of microfilament-rich ensheathing processes of the retinal pigment epithelium (RPE) and increased apparent adhesiveness between photoreceptors and RPE in explanted eyecups of Xenopus laevis. We have compared the time course of disc shedding and increased retinal adherence during L-glutamate treatment. Increased adherence was measured on the basis of the tendency of the apical RPE domains to partition with isolated neural retinas. In medium supplemented with L-glutamate (12 mM) or kainate (100 microM), a glutamate analog, the time course of increased partitioning of melanin pigment-rich cell fragments which contain ensheathing processes differs, even though the kinetics of induced disc shedding is the same in either case. Co-treatment with cytochalasin D (5 microM) completely blocks L-glutamate-induced disc shedding, as well as formation of microfilament-rich ensheathing processes, even though it has little effect upon apparent adhesiveness. The virtually complete dissociation of the effects of L-glutamate on disc shedding from that on increased adhesiveness of photoreceptors to RPE suggests that increased retinal adherence and pseudopod formation may be unrelated causally.

Adhesiveness↗
PubMed1995

Glutamate decarboxylase solubilized from the rat cerebral cortex by two different concentrations of Triton X-100: effects of glutamate analogues and analysis by SDS-PAGE/western blotting using GAD6 and K2 antibodies.

Analysis of two preparations (containing 0.1% and 0.5% Triton X-100) of glutamate decarboxylase (GAD) by Western blotting using GAD6 and K2 antibodies specifically recognizing two GAD isoenzymes, GAD65 and GAD67, respectively, indicated that the higher concentration of Triton X-100 at best only moderately favoured solubilization of GAD67. Several glutamate analogues were found to be either equally potent or equally inactive as inhibitors of glutamate decarboxylase activities in the two preparations. Among typical ligands for glutamate receptors and transporters, only quinolinic and L-cysteine sulphinic acids were weak inhibitors of GAD. Kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA), 3-((RS)-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), L-threo-3-hydroxy-aspartate, L-trans-pyrrolidine-2,4-dicarboxylate, dihydrokainate, kynurenic acid and N-methyl-D-aspartate were inactive. Even though the activity of glutamate decarboxylase in homogenates of rat cerebral cortex is higher at 0.5% than at 0.1% Triton X-100, structural requirements of the enzyme active site appear to be independent of Triton X-100 concentration. Furthermore, since the less soluble component of the enzyme activity contains about the same ratio of GAD65 to GAD67 as the more soluble one, it does not seem that the fractionation with Triton X-100 can be easily used to separate the two isoenzymes from each other.

Animals↗
PubMed1981

Evidence for compartmentalization of glutamate in rat brain synaptosomes using the glutamate sensitivity of phosphate-activated glutaminase as a functional test.

The glutamate content of rat brain synaptosomes was measured by high performance liquid chromatography to be 39 micromol/g protein. If uncompartmentalized this glutamate (4 mM) would inhibit phosphate-activated glutaminase considerably. Since the action of any endogenous effector on the enzyme is assumed to be negligible following disruption of the synaptosomes, due to dilution with the incubation medium, the inhibition by glumate and activation by phosphate were compared in intact and disrupted synaptosomes. The inhibition by endogenous glutamate in intact synaptosomes was found to correspond to less than that of 0.5 mM of added glutamate to disrupted synaptosomes, indicating that the major fraction of synaptosomal glutamate is compartmentalized.

Animals↗
PubMed1988

Prolonged time course of glutamate-operated single channel currents in neuromuscular preparations of small crayfish and a membrane current triggered by glutamate channel gating.

Single channel currents activated by glutamate were recorded by means of the patch-clamp technique in the abdominal superficial extensor muscle and the claw opener muscle of small (1-3 months old) and large (greater than 16 months old) crayfish. It was found that in small crayfish the time course of glutamate-operated single channel currents was prolonged by a factor of about 4 in these two preparations. In the abdominal superficial extensor muscle, single channel currents activated by 5 mmol/l glutamate had a mean burst length of tau = 2-3 ms in large crayfish and a mean burst length of tau = 8-9 ms in small crayfish. In the claw opener, for large crayfish tau congruent to 0.5 ms and for small crayfish tau = 1.5-2.5 ms resulted (500 mumol/l glutamate). Moreover, single channel currents with long time courses often slowly increased their amplitudes during the open time of the channel and current amplitudes did not decline completely to the baseline after channel closing. In addition, single channel currents with relatively constant amplitude were often followed by a small increasing and decreasing membrane current. The latter results suggest that glutamate channel gating might trigger a membrane current.

Animals↗
PubMed1994

Involvement of the glutamate receptor delta 2 subunit in the long-term depression of glutamate responsiveness in cultured rat Purkinje cells.

An antisense oligonucleotide against the glutamate receptor delta 2 subunit mRNA, which is selectively expressed only in Purkinje neurons, suppressed the induction of long-term depression (LTD) of glutamate responsiveness in the rat cerebellar culture. LTD of glutamate response is induced by pairing glutamate application and depolarization of a Purkinje cell. Treatment of the culture with the antisense oligonucleotide exerted no appreciable effect on basic physiological and morphological properties of Purkinje cells, except for LTD induction and reduction of delta immunoreactivity which was intense in distal dendrites. Sense and missense oligonucleotides, which were used as controls, did not block LTD induction. These results suggest that the glutamate receptor delta 2 subunit is involved in the cerebellar LTD.

Action Potentials↗
PubMed1993

Determination of L-glutamate and L-glutamine in pharmaceutical formulations by amperometric L-glutamate oxidase based enzyme sensors.

An amperometric biosensor for the direct determination of L-glutamate was developed by chemical bonding of L-glutamate oxidase (GAO) on a carboxylic Nylon membrane with polyazetidine prepolymer (PAP), and using a hydrogen peroxide electrode as indicating sensor. The biosensor is specific for L-glutamate and the peculiar analytical properties (linearity range, reproducibility, accuracy) were experimentally determined. Furthermore, the same basic biosensor was also modified to be used and characterized for the direct determination of L-glutamine. This L-glutamine biosensor was obtained by coimmobilizing, on two separate membranes, glutamic acid oxidase and glutaminase (GMN) on the same biosensor. The two sensors were then used for the determination of glutamate and L-glutamine contained in pharmaceutical formulations and the results were compared with those obtained by other analytical methods.

Amino Acid Oxidoreductases↗
PubMed2006

Glutamate optical biosensor based on the immobilization of glutamate dehydrogenase in titanium dioxide sol-gel matrix.

A simple and novel titania sol-gel derived optical biosensor coupled with carboxy seminaphthorhodamine-1-dextran (SNARF-1-dextran) as the fluorescent dye was fabricated for the determination of glutamate in water and biological samples. The NADH-dependent glutamate dehydrogenase (GLDH) was trapped in titania sol-gel derived matrix prepared by vapor deposition method. In addition, scanning electron microscopy (SEM) and atomic force microscopy (AFM) were used to characterize the surface morphology of the spots. SEM and AFM images showed that the deposition of titania precursor at 27 degrees C for 6.5h was found to be suitable to form transparent titania sol-gel matrix to encapsulate GLDH and fluorescent probe. AFM images showed that the roughness of TiO(2) surface increased from 2.16 nm in the absence of GLDH and SNARF to 37.8 nm after the immobilization. The developed titania biosensor has good analytical performance with water samples. A dynamic range between 0.04 and 10mM with the detection limit of 5.5 microM were observed. The responses to glutamate in biological samples also showed good performances, and the dynamic range and detection limit were 0.02-10mM and 6.7 microM, respectively. High precision with relative standard deviations of 4.2 and 10.7% in water and biological samples, respectively, were also demonstrated. In addition, the biosensor showed a relatively high storage stability over more than 1 month. Results obtained in this study clearly demonstrate that this simple vapor deposition method can be successfully used to form transparent titania sol-gel film for the fabrication of glutamate biosensors that are suitable for optical detection of glutamate in water and biological samples.

Biosensing Techniques↗
PubMed2006

Glutamate receptor-mediated inhibition of L-glutamate efflux from cerebral cortex in vitro.

We tested whether glutamate receptor ligands affect oxygen-glucose deprivation-evoked L-glutamate efflux from adult rat cerebrocortical prisms. The uncompetitive NMDA antagonist AR-R15896AR inhibited efflux (IC50 34 microM, 87% maximal inhibition). AMPA/kainate receptor blockade (NBQX, 100 microM) or Group II metabotropic glutamate receptor activation (DCG-IV, 10 microM) inhibited efflux (41%, 67% respectively) but Group I mGluR blockade (CPCCOEt/MPEP, 10 microM) was without effect. These data support a modulatory effect of glutamate receptors on L-glutamate efflux.

Animals↗
PubMed1998

Changes in extracellular glutamate and GABA levels in the hippocampal CA3 and CA1 areas and the induction of glutamic acid decarboxylase-67 in dentate granule cells of rats treated with kainic acid.

For the evaluation of glutamatergic and GABAergic transmission during seizures, rat hippocampal CA1 and CA3 areas were separately assessed by brain microdialysis, and extracelluar glutamate and GABA were measured through the course of the seizures after a systemic administration of kainic acid (KA). The generalized convulsion started at about 1.5 h and was suppressed by diazepam at 2 h after the KA treatment. In the CA3 area, extracellular glutamate started to increase soon after the KA injection and returned to the control level at about 1.5 h. A decrease and then slight increase of the extracellular glutamate level in CA3 followed the diazepam injection. In the CA1 area, in contrast, a long-lasting decrease of extracellular glutamate was observed. The extracellular GABA concentration in the CA3 area increased immediately after the systemic administration of KA and returned to the normal level at about 3.5 h. A second increase in the extracellular GABA in this area began at about 4.5 h after the KA treatment. In the CA1 area, an increase of extracellular GABA began at about 3.5 h after KA administration (much later than that observed in the CA3 area) and was maintained throughout the observation. In situ hybridization showed a transient expression of glutamic acid decarboxylase (GAD)-67 mRNA in the granule cell layer of the dentate gyrus at 4 and 6 h, whereas GAD65 mRNA was unaffected. GABA immunoreactivity in the same area and mossy fibers in the CA3 were increased most significantly at 8 h after administration of KA. The possible relation of GABA induction in mossy fibers with the delayed increase in extracellular GABA in CA3 was discussed.

Analysis of Variance↗
PubMed1998

Anticonvulsant and glutamate release-inhibiting properties of the highly potent metabotropic glutamate receptor agonist (2S,2'R, 3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV).

The anticonvulsant effects of intracerebral administration of the highly potent group II metabotropic glutamate receptor agonist, DCG-IV, were tested in fully kindled rats following daily electrical stimulation of the basolateral amygdala. The agonist caused a dose-dependent increase in the generalized seizure threshold (GST) of these seizure susceptible animals within the dose range tested (0. 01-1.0 nmol). The estimated GST100 value (dose causing a 100% increase in GST) for this effect was 0.22 nmol. The anti-seizure activity of DCG-IV was fully inhibited in the presence of the group II metabotropic glutamate receptor antagonist (2S,1'S, 2'S)-2-methyl-2-(carboxycyclopropyl)glycine (MCCG; 40 nmol), while MCCG alone showed no significant inhibitory effect on seizure activity. DCG-IV also powerfully inhibited depolarization-induced release of [3H]D-aspartate from rat cerebrocortical synaptosomes, with an IC50 value of 0.39 microM. In this respect, DCG-IV was approximately 70-fold more potent than the clinically effective anticonvulsant drug lamotrigine (IC50=27.7 microM), a proposed neurotransmitter release inhibitor known to inhibit glutamate release, also tested in this assay. These findings demonstrate the high potency of DCG-IV as an anticonvulsant agent and confirm a key role for group II metabotropic glutamate receptors in the control of seizure activity via their modulatory action on neuronal glutamate release.

Amygdala↗
PubMed2000

Inhibition of synaptosomal [3H]glutamate uptake and [3H]glutamate binding to plasma membranes from brain of young rats by glutaric acid in vitro.

Synaptosomes and plasma membrane preparations from brain of 30-day-old rats were incubated with glutaric acid at final concentrations ranging from 10 nM to 1 mM for the determination of glutamate uptake and binding, respectively. [3H]Glutamate uptake into synaptosomes was inhibited by approximately 50% by 1 mM glutaric acid, corresponding to the concentration found in brain of glutaric acidemic children. In addition, in the presence of extracellular Na+ concentrations, the same dose of glutaric acid decreased by about 30% [3H]glutamate binding to brain plasma membranes. The results indicate that the inhibition of both glutamate uptake into synaptosomes and glutamate binding to plasma synaptic membranes by the metabolite could result in elevated concentrations of the excitatory neurotransmitter in the synaptic cleft, potentially causing excitotoxicity to neural cells, a fact that may be related to the brain damage characteristic of glutaric acidemia type I.

ATP-Binding Cassette Transporters↗
PubMed2000

Effect of ionotropic glutamate receptors antagonists on the modifications in extracellular glutamate and aspartate levels during picrotoxin seizures: a microdialysis study in freely moving rats.

Our previous studies have shown a local decrease in glutamate and aspartate levels during seizures, induced by picrotoxin microdialysis in the hippocampus of chronic freely moving rats. In this paper, we study the effect of continuous hippocampal microperfusion of the NMDA, AMPA and kainate glutamate receptor inhibitors 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine (MK-801); 6,7-dinitroquinoxaline-2,3-dione (DNQX), and 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466). We also examine the action of L(-)-threo-3-hydroxyaspartic acid (THA), a glutamate and aspartate reuptake blocker, on the modification of extracellular glutamate and aspartate levels induced by picrotoxin, using the microdialysis method in freely moving rats. We found that changes in extracellular hippocampal concentrations in both amino acids are prevented by NMDA, AMPA and kainate receptor inhibitors. Seizures elicited under DNQX also induce a transient increase in aspartate extracellular levels coincident with seizure time. L(-)-threo-3-hydroxyaspartic acid increased the basal extracellular concentrations of both amino acids, but did not prevent the seizure-related decrease. Our results suggest that glutamate, the major neurotransmitter at the synaptic level, may also play an important role in non-synaptic transmission during seizures.

Animals↗