Disease relevance of glutamate

• Stratification of patients into those with and without macroscopic emphysema (EMPH+, EMPH-, respectively), with comparable physical activity levels on the basis of previous observations, revealed lower values for La threshold and GLU in EMPH+ patients [1].
• This study illustrates that the early lactic acidosis during exercise in patients with COPD is associated with the physical inactivity-related reduction in these patient's muscle GLU [1].
• Carbon monoxide metabolism of the methylotrophic acidogen Butyribacterium methylotrophicum [2].
• Dry/wet heart weight ratios were also greater in GGA (0.20), when compared with G2 (0.16), GX (0.17), GM (0.17), GM (0.17), and GL (0.17) (all p < 0.02), suggesting less cellular/interstitial edema [3].
• Reperfusion arrhythmia (in sec) was significantly (all p < 0.05) shorter in GGA (115 +/- 33) vs G1 (315 +/- 29) and G2 (273 +/- 33), and also in GL (161 +/- 26) vs G1 [3].
• Glutamate release from VMH neurons is an important component of the neurocircuitry that functions to prevent hypoglycemia [4].
• Glioma cells release glutamate in sufficient quantities to activate AMPA-Rs on themselves or neighboring cells, thus acting in an autocrine and/or paracrine fashion [5].
• Cerebral ischemia is associated with an excessive release of glutamate, and in postischemic cerebral edema ablation of AQP4 attenuates the degree of damage [6].
• Glutamate deprivation or blockade decreased prostate cancer cells' proliferation, migration, and invasion and led to apoptotic cell death [7].

Psychiatry related information on glutamate

• BOD estimations for the GGA standard resulted in an extended linear range: 2-100 mg/l. Response reproducibility was +/-10% for a GGA standard containing 10 mg BOD/l. For analysis of pulp mill effluents, the BOD detection limit was 2 mg/l with a response time of 5 min [8].
• These data suggest that glutamate receptor expression is altered in the medial temporal lobe in schizophrenia and the mood disorders [9].
• This study suggests that glutamate plays a role in the pathophysiology of bipolar disorder and major depression [10].

High impact information on glutamate

• At the molecular level, LTD appears to be caused by desensitization of receptor molecules in PC dendrites towards the PF neurotransmitter, presumably L-glutamate (Glu) [11].
• Decreases in the current threshold for locomotion produced by electrical stimulation of the MRF were observed when the MRF was infused with either GA (40-80 nmol), DL-homocysteic acid (DL-HCA; 200 nmol), or picrotoxin (PIC; 15 nmol) [12].
• The COPD group had lower values for La threshold and muscle GLU, and higher values for muscle La and pyruvate levels than did the PI group [1].
• The minor alternative transcript skips both exon 2 and exon 3 (FVII Delta 2, 3), leading to an in-frame deletion of the propeptide and gamma-carboxylated glutamic acid (Gla) domains of mature FVII protein [13].
• In the vertebrate CNS, Gly acts both as an inhibitory neurotransmitter and as a Glu modulator or coagonist at postsynaptic N-methyl-D-aspartate (NMDA) receptors [14].

Chemical compound and disease context of glutamate

• Stereochemical course of the decarboxylation of (S)-glutamic acid by glutamate decarboxylase from Escherichia coli (E.C. 4.1.1.15) [15].
• In the present study, the protective effects of Puerarin (Pur) on cerebral injuries evoked by ischemia/reperfusion was supported by a decrease of extracellular amino acids, especially glutamate (Glu), which were monitored by microdialysis combined with HPLC throughout the experiments [16].

Biological context of glutamate

• The maximal extent of inhibition (1 mM) was both amino acid-dependent (IC50: NMDA, 5 microM; KA, 3.3 microM; QUIS, 47 microM; GLU, greater than 1 mM) [17].
• The pretreatment of BT-11 (0.5, 3, and 5 micro g/ml) significantly reduced cell death induced by Glu (1 mM), A beta (10 micro M) and CT105 (10 micro M) in a dose-dependent manner [18].
• Cell survival was reduced to 31% in GLU-treated neuronal cultures; PKC inhibitors were not able to modify this effect [19].
• The application of Ka (1 x 10(-8) to 1 x 10(-6) M), NMDA (1 x 10(-8) to 1 x 10(-4) M), Quis (1 x 10(-7) to 1 x 10(-4) M), Glu (1 x 10(-5) to 5 x 10(-4) M), and Asp (1 x 10(-5) to 5 x 10(-3) M) enhanced the oxygen consumption dose-dependently, to a maximum of 120-146% of the resting level (8.43 mumol/g protein/min) [20].
• These results support the proposal that the D-aspartate-insensitive Glu binding site is somehow related to an amino acid receptor-mediated modulation of dopaminergic transmission in the rat corpus striatum [21].

Anatomical context of glutamate

• It is generally agreed that (S)-glutamic acid (Glu) receptors are involved in the development of a number of diseases in the central nervous system (CNS), and ligands that interact with these receptors are of significant interest [22].
• After a behavior test,the levels of glutamate (Glu) and GABA in the frontal cortex and hippocampus were assessed using high-performance liquid chromatography (HPLC) [23].
• The aim of this study was to assess the synovial fluid (SF) neurotransmitter excitatory amino acid (EAA) levels, including glutamate (Glu) and aspartate (Asp), in the context of SF levels of other amino acids, TNF-alpha and chemokines from patients with active arthropathies [24].
• The Glu uptake into oocytes was higher in mRNA-injected oocytes than in vehicle-injected ones [25].
• Treatment with DEP produced significant changes in the levels of Asp in the hypothalamus (Ht) and cortex (Cx); Glu in the Ht, Cx, midbrain (Mb), and striatum (S); and Gln in the Cx [26].

Associations of glutamate with other chemical compounds

• A colocalization of Gly transporters and NMDA receptors has been reported in brain tissue (Smith et al. Neuron 8:927-936, 1992); since the concentration of Gly could participate in the modulation of Glu excitatory transmission in the vertical pathways of the retina, transport of Gly in monolayer cultures of Müller cells was studied [14].
• Homo-AMPA (8), which is a 3-isoxazolol bioisostere of 2-aminoadipic acid (3), was, however, shown to be a specific and rather potent agonist at mGlu6, approximately 4 times weaker than the nonselective excitatory amino acid receptor agonist (S)-glutamic acid [27].
• Endogenous GLU release from OGD slices increased to about 15 times the basal values after 15 min of oxygen-glucose deprivation, and to 25 and 35 times the basal level in the presence of the PKC inhibitors staurosporine (0.1 microM) and bisindolylmaleimide (1 microM), respectively [19].
• Using the high-affinity mutant (E363D) of bovine retinal CNG channel in which the Glu at position 363 was replaced to Asp, we constructed tandem dimers and investigated the binding characteristics of divalent cations to the site [28].
• This regulatory mechanism by the bifunctional enzyme RocG allows the tight control of glutamate metabolism by the availability of carbon and nitrogen sources [29].
• Treating cells with EGTA-AM plus wortmannin essentially abolished Thr-dependent glutamate efflux [30].
• Either Nedd4 or PTEN knockdown with small interfering RNA prevented the morphine-induced EAAC1 degradation and decreased glutamate uptake [31].
• Moreover pinacidil, diazoxide, and iptakalim reversed the inhibition of glutamate uptake induced by 1-methyl-4-phenylpyridinium (MPP+) [32].
• Glutamate activation of N-methyl-D-aspartate (NMDA) receptors in the MPOA is at least partly responsible for behavioral effects evoked by increase glutamate [33].
• This conformation is stabilized by contacts between large hydrophobic patches in the R2 domain that are absent in NMDA receptors, suggesting that the ATDs of individual glutamate receptor ion channels have evolved into functionally distinct families [34].
• With the non-bovine serum albumin brain and heart mitochondria oxidizing succinate, the addition of pyruvate and glutamate abrogated inhibition of Complex II by oxaloacetate [35].

Gene context of glutamate

• Added Glu resulted in significantly increased TNF-alpha levels in primary synovial cell cultures [24].
• The data indicate that substitution for Glu in an antifolate by some Glu analogs in which the gamma-COOH is either altered or replaced (e.g., gamma-tetrazole-Glu) leads to loss of both FPGS substrate activity and binding; antifolate target specificity is unchanged, while uptake is actually enhanced [36].
• Percent recovery in PLVP was improved (p < 0.03) in GL (81 +/- 2) and GGA (81 +/- 2) vs. G2 (71 +/- 3), without significant alterations in oxygen consumption [3].
• Microinjection of 4-10 nl of 0.18 M Glu in 30 of 39 explored sites at the T2 level elicited significant increases in HR (+24.2 +/- 3.1 beats/min) [37].
• These findings demonstrate that the cell response to OGD and GLU involves PKC in a complex way [19].
• All these data show that the GLT1/EAAT2 glutamate transporter is a target gene of PPARgamma leading to neuroprotection by increasing glutamate uptake [38].
• We show that mice deficient in the glutamate transporters GLAST or EAAC1 demonstrate spontaneous RGC and optic nerve degeneration without elevated IOP [39].
• Inhibition of N-methyl-D-aspartate (NMDA) receptors in RA FLS increased proMMP-2 release, whereas non-NMDA ionotropic glutamate receptor antagonists reduced IL-6 production by these cells [40].

Analytical, diagnostic and therapeutic context of glutamate

• Western blot analysis of GLU-treated cortical neurons showed a significant decrease only in the total level of beta(2) isoforms [19].
• In the rest of microinjections Gly and Glu produced changes of SAP and VNA in different combinations [41].
• The adsorption of the amino acid, (S)-glutamic acid, was investigated on Ag{110} as a function of coverage and adsorption temperature using the techniques of scanning tunneling microscopy, low energy electron diffraction, and reflection absorption infrared spectroscopy [42].

References