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Query: CAS:6893-26-1 (glutamate)
 73,096 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamic acid has been believed to be an excitatory transmitter in the mammalian central nervous system (CNS), and has been implicated in the pathogenesis of neuronal damage in the mammalian CNS. There are two major classes of glutamate receptors, ionotropic (iGluR) and metabotropic glutamate receptors (mGluR). Participation of iGluRs in glutamate mediated neurotoxicity has been well documented. However, much less is known about participation of mGluRs than the case for iGluRs. The physiological roles of mGluRs have been believed to regulate transmitter release and to modulate the function of iGluRs through activating various intracellular second messenger system. Recently we have discovered several potent agonists for mGluRs which would provide additional information about glutamate mediated neurotoxicity. DCG-IV, one of the most potent mGluR agonists, alleviated kainate-induced limbic motor seizures in extremely low doses in the rat, but the dose response curves showed a bell typed one. DCG-IV also demonstrated severe sedative condition and markedly prolonged the sleeping time in halothane anesthesia. DCG-IV depressed the duration of after-discharges and the seizures evoked by electrical stimulation in the amygdala kindling rat. DCG-IV significantly decreased in number of kainate-induced degenerated neurons in the area of hippocampal CA1, amygdala and septum when DCG-IV was continuously applied into the ventricule. In conclusion, activation of mGluRs leads the alleviation of neuron damage induced by iGluR agonists.
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PMID:[Excitatory amino acids and neuronal death]. 772 52

Coryneform bacteria are widely used to produce amino acids, in particularly glutamic acid, by fermentation. To study the metabolic fate of glucose as the carbon source, we developed a method to analyze intracellular extracts by NMR and HPLC. The intracellular metabolites represent the metabolic state of the cells. Glutamic acid was the major metabolic intermediate found in the extracts and its 13C isotopic enrichment reflected that of pyruvic acid. Thus, it was possible to determine the respective contributions of the two major glucose catabolic pathways during the exponential growth phase; glycolysis (55%) and the pentose phosphate pathway (45%). Absolute glutamate 13C enrichments resulting from the incorporation of [1-13C]glucose were determined to quantify the contribution of several metabolic pathways such as anaplerotic pathways (61%; phosphoenolpyruvate carboxylase, pyruvate carboxylase, malic enzyme), a single turn (32%) or multiple turns of the Krebs cycle and the glyoxylate shunt, to oxaloacetate synthesis. A previously described model was adapted to C. melassecola for these calculations. The Krebs cycle was active, whereas the glyoxylate shunt was inactive in exponentially growing cells of C. melassecola with glucose as the sole carbon source. The contributions of anaplerotic enzymes and pyruvate dehydrogenase to replenishing the Krebs' cycle were determined to be 38% and 62%, respectively.
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PMID:13C-NMR studies of Corynebacterium melassecola metabolic pathways. 785 27

Glutamic acid and glycine were quantified in cells and medium of cultured rostral rhombencephalic neurons derived from fetal rats. In the presence of 1 mM Mg2+, NMDA (50 microM) significantly stimulated (by 69%) release of newly synthesized 5-[3H]hydroxytryptamine ([3H]5-HT). D-2-Amino-5-phosphonopentanoate (AP-5; 50 microM) blocked the stimulatory effect of NMDA. AP-5 by itself inhibited [3H]5-HT release (by 25%), suggesting a tonic control of 5-HT by glutamate. In the absence of Mg2+, basal [3H]5-HT release was 60% higher as compared with release with Mg2+. AP-5 blocked the increased [3H]5-HT release observed without Mg2+, suggesting that this effect was due to the stimulation of NMDA receptors by endogenous glutamate. Glycine (100 microM) inhibited [3H]5-HT release in the absence of Mg2+. Strychnine (50 microM) blocked the inhibitory effect of glycine, indicating an action through strychnine-sensitive inhibitory glycine receptors. The [3H]5-HT release stimulated by NMDA was unaffected by glycine. In contrast, when tested in the presence of strychnine, glycine increased NMDA-evoked [3H]5-HT release (by 22%), and this effect was prevented by a selective antagonist of the NMDA-associated glycine receptor, 7-chlorokynurenate (100 microM). 7-Chlorokynurenate by itself induced a drastic decrease in [3H]5-HT release, indicating that under basal conditions these sites were stimulated by endogenous glycine. These results indicate that NMDA stimulated [3H]5-HT release in both the presence or absence of Mg2+. Use of selective antagonists allowed differentiation of a strychnine-sensitive glycine response (inhibition of [3H]5-HT release) from a 7-chlorokynurenate-sensitive response (potentiation of NMDA-evoked [3H]5-HT release).
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PMID:N-methyl-D-aspartic acid/glycine interactions on the control of 5-hydroxytryptamine release in raphe primary cultures. 790 29

Glutamic acid, an excitatory neurotransmitter, was monitored in vivo in the corpus striatum of freely moving rats by brain microdialysis and capillary electrophoresis with laser-induced fluorescence detection. A procedure to derivatize glutamate in complex matrices was developed. Capillary electrophoresis in 12 microns I.D. capillaries was performed to determine glutamate with a migration time of 195 s. Laser-induced fluorescence detection with 488-nm radiation from an argon ion laser and with colinear geometry was used. An injection of haloperidol decreased the concentration of glutamic acid in the dialysates. These experiments support the hypothesis that dopamine receptor blockade decreases glutamate release. The potential of these techniques for the study of chemicals in biomedical experiments is discussed.
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PMID:In vivo monitoring of glutamate in the brain by microdialysis and capillary electrophoresis with laser-induced fluorescence detection. 790 17

Glutamic acid dimethyl ester (GME; 3.0-10.0 mM) enhanced insulin release evoked by 6.0-8.3 mM D-glucose, 1.0-10.0 mM L-leucine, or 5.0-10.0 mM 2-amino-bicyclo(2,2,1)heptane-2-carboxylic acid, causing a shift to the left of the sigmoidal relationship between insulin output and D-glucose concentration. In the absence of D-glucose, GME also unmasked the insulinotropic potential of glibenclamide. In islets exposed to L-leucine, the insulinotropic action of GME coincided with an early fall and later increase in 86Rb outflow and augmentation of 45Ca outflow from prelabeled islets. The measurement of O2 uptake, NH4+ output, production of 14CO2 from islets prelabeled with [U-14C]palmitate, generation of 14C-labeled amino acids and 14CO2 from the dimethyl ester of either L-[1-14C]glutamic acid or L-[U-14C]glutamic acid, and D-[2-14C]glucose as well as D-[6-14C]glucose oxidation in the presence or absence of GME indicated that the latter ester was efficiently converted to L-glutamate and its further metabolites. The overall gain in O2 uptake represented the balance between GME oxidation and its sparing action on the catabolism of endogenous fatty acids and exogenous D-glucose. It is proposed that GME might represent a new tool to bypass beta-cell defects in D-glucose transport, phosphorylation, and further metabolism and, hence, to stimulate insulin release in experiments conducted in animal models of non-insulin-dependent diabetes mellitus.
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PMID:Insulinotropic action of glutamic acid dimethyl ester. 794 7

Glutamic acid has been believed to be an excitatory transmitter in the mammalian central nervous system (CNS), and it has been implicated in the pathogenesis of neuronal damage in the mammalian CNS. There are two major classes of glutamate receptors, ionotropic (iGluR) and metabotropic glutamate receptors (mGluR). Participation of iGluRs in glutamate-mediated neurotoxicity has been well documented; however, much less is known about the participation of mGluRs than the case for iGluRs. The physiological roles of mGluRs have been believed to regulate transmitter release and to modulate the function of iGluRs through activating various intracellular second messenger systems. Recently we have discovered several potent agonists for mGluRs that would provide additional information about glutamate-mediated neurotoxicity. In the present paper, we describe the pharmacological profiles of these mGluR agonists.
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PMID:[Excitatory amino acid receptors]. 795 10

Glutamic acid metabolism in 24-hour starved 20-day pregnant and control non-pregnant rats, following intravenously administered [14C]-glutamic acid has been studied. The utilization of glutamate as a gluconeogenic precursor is not increased in late pregnancy under 24-hour starvation and it is regulated by the lower blood substrate availability. In addition, the steady state levels of glutamate, glutamine, aspartate, protein and glucose in blood, liver and skeletal muscle, together with tissue glycogen and lipids and metabolite composition pools, are given for both non-pregnant and pregnant rats.
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PMID:"In vivo" glutamic acid metabolism in late pregnant rats. 810 12

Glutamic acid plays an important role as a main excitatory amino acid and also as one of the central metabolites in the central nervous system (CNS). This amino acid also acts as a toxic substance in the vertebrate CNS, including the retina, especially in ischemic conditions. This paper reviews recent advances in retinal research on glutamate metabolism and its relationship with pathogenesis of retinal diseases. Excessive administration of glutamate induces overstimulation of N-methyl-D-aspartate (NMDA) and non-NMDA receptors, and influx of Na+, Cl-, and water to postsynaptic elements, causing lysis and swelling. In hypoxic or ischemic conditions, accumulation of glutamate was observed in most parts of the retina. Morphological and functional changes induced by ischemia could be prevented by preadministration of an antagonist of NMDA receptors. These results suggest that the same pathological mechanism as in the CNS exists in the retina. They also suggest that a new pharmacological approach for treating retinal abnormalities caused by ischemia could be introduced in the ophthalmology clinic in the near future. Abnormality of glutamate dehydrogenase, an important enzyme in the glutamate metabolism, has been reported in patients with spinocerebellar degenerations. Retinal dystrophy was also reported in some of them. Partial deficiency of heat-labile activity of this enzyme has been reported to be profoundly related with those patients with retinal abnormalities. This suggests that not only glutamate itself, but also abnormalities in its metabolic path way might be deeply correlated with the pathogenesis of retinal degeneration.
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PMID:[Dual nature of excitatory amino acids in the vertebrate retina]. 819 8

Chemical modification and proteolytic digestion studies have identified a transmembrane glutamic acid residue (E953) of the alpha subunit of the pig kidney Na, K-ATPase as a possible cation binding site [Goldshleger et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 6911-6915]. In addition, an adjacent glutamate (E954) is conserved in all species and isoforms and may also be involved in cation binding. To further explore the role of these residues in ion transport, we have utilized a mutagenesis-expression strategy. This approach avoids the introduction of a large chemical moiety into the protein and allows specific amino acid substitutions to be introduced. Glutamic acid residues 955 and 956 of the rat alpha-1 subunit (corresponding to glutamates 953 and 954 of the pig kidney Na, K-ATPase) were replaced separately and together using site-directed mutagenesis of the rat alpha-1 cDNA. The mutant cDNAs were expressed in ouabain-sensitive HeLa cells. This system makes it possible to rapidly identify amino acid substitutions which significantly impair enzyme function, as substitutions which do not affect enzyme activity will yield colonies in the presence of ouabain, while substitutions which severely impair function will prevent or limit growth of the ouabain-sensitive HeLa cells. The amino acid replacements (E955Q, E956Q, E955Q-E956Q, E955D-E956D) all resulted in the growth of ouabain-sensitive cells, demonstrating that the modified Na, K-ATPase in each case was functional. To further study the altered enzymes, ouabain-resistant colonies were isolated and expanded into stable cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Site-directed mutagenesis of a predicted cation binding site of Na, K-ATPase. 838 Jul 10

Transport of glutamic acid by the choroid plexus, the blood-cerebrospinal fluid (CSF) barrier, was investigated by using the isolated choroid plexi from the fourth (FVCP) and lateral ventricles (LVCP) of the young adult miniswine in vitro. Glutamic acid uptake was very pronounced, with concentrations 7-fold (LVCP) and 2.4-fold (FVCP) higher in tissue than in medium after only 5 min of incubation with 1 microM glutamic acid. Tissue/medium ratios reached steady state by 15 min at 30-fold (LVCP) and 11-fold (FVCP). Uptake was energy-dependent and inhibited by ouabain and hypothermia. L-Aspartic acid was shown to be inhibitory in a concentration-dependent manner, suggesting that it shares a common transport system, whereas neither octanoic acid nor okadaic acid (transported by a separate fatty acid system) inhibited glutamic acid transport. At the same temperature, the labeled metabolite of glutamate (glutamine) in the tissue was 64.7%, 73.2%, and 72.5% of total radioactivity at 5, 30, and 60 min, respectively. The estimated Km values for glutamate uptake by the choroid plexus are 264 microM (FVCP) and 196 microM (LVCP); Vmax values are 87 (FVCP) and 147 (LVCP) nmol/g/min, respectively. These results indicate that, in addition to the metabolism of glutamate to glutamine, an active uptake mechanism is present in the choroid plexus of miniswine which may serve to regulate glutamic acid concentration in the CSF.
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PMID:Kinetic analysis of glutamate transport by the miniswine choroid plexus in vitro. 886 57


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