EAAT2UptakeNeuronalEAATActivity of glutamateGABAVGluT2NeuronsExcitatory amino acid transpExtracellular spaceMetabotropic glutamateAspartateGlutamatergicAstrocyticPlasma membraneVesicular glutamateReceptors and transportersMetabolismNeurotransmitter glutamateMajor excitatory neurotransmitterHigh-affinityEAAT3SynapsesVitroEAATsConcentrationsRegulationPresynapticAstrocytesGeneMembraneKinaseArchaealSubtypesProteins
EAAT28
- EAAT2 is responsible for over 90% of glutamate reuptake within the central nervous system (CNS). (wikipedia.org)
- Jensen and Bauner-Osborne (2004) Pharmacological characterization of human excitatory amino acid transporters EAAT1, EAAT2 and EAAT3 in a fluorescense-based membrane potential assay. (tocris.com)
- Abstract Recent evidence suggests that the predominant astrocyte glutamate transporter, GLT-1/ Excitatory Amino Acid Transporter 2 (EAAT2) is associated with mitochondria. (brad.ac.uk)
- The Excitatory Amino Acid Transporter 2 (EAAT2) accounts for 80% of brain glutamate clearance and is mainly expressed in astrocytic perisynaptic processes. (unige.it)
- Taken together, our results demonstrate that pathogenic LRRK2 interferes with the physiology of EAAT2, pointing to extracellular glutamate overload as a possible contributor to neurodegeneration in PD. (unige.it)
- Gene expression of glial glutamate transporter EAAT2 and the predominantly neuronal glutamate transporter EAAT3 were examined by in situ hybridization. (cshl.edu)
- Other compounds that enhance the activity of EAAT2 (the main astrocytic transporter in the CNS) in pathological conditions, such as ß-lactam antibiotics, attenuate damage in both acute and chronic neurodegenerative disorders. (drexel.edu)
- Previous studies in my lab have identified a unique natural compound from the spider Parawixia bistriata that increases the activity of glutamate transporter EAAT2 and has neuroprotective effects on retinal tissue under ischemia. (drexel.edu)
Uptake13
- Potent competitive inhibitor of L-glutamate uptake. (tocris.com)
- In neurons, glucose uptake is facilitated by a family of glucose transporters (GLUTs) with the GLUT1 and 3 isoforms believed to be responsible for the majority of glucose uptake within the brain (Duelli and Kuschinsky, 2001). (jneurosci.org)
- 2000) Uptake of glutamate into synaptic vesicles by an inorganic phosphate transporter. (guidetopharmacology.org)
- METHODS: A dual-isotope (l-[3H]glutamate and [14C]GABA) approach allowed simultaneous comparisons of anesthetic effects on three independent assays of glutamate and GABA transporters in adult rat cerebral cortex: transmitter uptake into isolated nerve terminals (synaptosomes), transmitter binding to lysed and washed synaptosomes (synaptic membranes), and carrier-mediated release (reverse transport) of transmitter from preloaded synaptosomes using a modified superfusion system. (cornell.edu)
- RESULTS: Isoflurane produced small but statistically significant inhibition of l-[3H]glutamate and [14C]GABA uptake, while propofol had no effect. (cornell.edu)
- Inhibition of uptake by isoflurane was noncompetitive, an outcome that was mimicked by indirectly affecting transporter function through synaptosomal depolarization. (cornell.edu)
- Volatile anesthetics (VAs) have been demonstrated to enhance the uptake of glutamate in in vitro systems. (silverchair.com)
- The system A inhibitor MeAIB (amethylamino-iso-butyric acid) reduces neuronal uptake of glutamine with concomitant reduction in intracellular glutamate concentrations, indicating that SAT2-mediated glutamine uptake can be a prerequisite for the formation of glutamate. (dadospdf.com)
- Chronic exposure of cultured PC12 cells to neurotoxins, such as 6-OHDA, MPP + , or rotenone, decreased overall [ 3 H]-glutamate uptake in a concentration-dependent manner. (arizona.edu)
- Pre-treatment using 10 μM Ipt significantly protected cells against neurotoxin-induced glutamate uptake diminishment, and this protection was abolished by the K ATP channel blocker glibenclamide (20 μM), suggesting that the protective mechanisms may involve the opening of K ATP channels. (arizona.edu)
- In 6-OHDA-treated rats (as an in vivo Parkinson's disease model), [ 3 H]-glutamate uptake was significantly lower in synaptosomes isolated from the striatum and cerebral cortex, but not the hippocampus. (arizona.edu)
- Pre-conditioning using 10, 50, and 100 μM Ipt significantly restored glutamate uptake impairment and these protections were abolished by blockade of K ATP channels. (arizona.edu)
- Regulation of glutamate, GABA and dopamine transporters' uptake, surface mobility and expression. (albany.edu)
Neuronal8
- Expression levels of the primary neuronal glucose transporters (GLUTs) isoforms 1, 3, 4, and 8 were found to be unaltered within a 24 h period after excitation. (jneurosci.org)
- Excessive glutamate release and the overexcitation of glutamate receptors has been identified as a central mediator in the pathophysiology of the neuronal injury associated with ischemic stroke and head trauma ( Choi, 1987 ). (jneurosci.org)
- Neuronal influences are necessary to produce mitochondrial co-localization with glutamate transporters in astrocytes. (brad.ac.uk)
- Ugbode C, Hirst WD and Rattray M (2014) Neuronal influences are necessary to produce mitochondrial co-localization with glutamate transporters in astrocytes. (brad.ac.uk)
- CONCLUSIONS: These findings suggest that isoflurane and propofol at clinical concentrations do not affect excitatory glutamatergic transmission or inhibitory GABAergic transmission directly effects on their presynaptic neuronal transporters. (cornell.edu)
- Dysfunction of glutamate transporters causes glutamate accumulation that results in glutamate-mediated neuronal injury, which has been implicated in the pathophysiology of ischemic brain damage and other neurodegenerative disorders, such as amyotrophic lateral sclerosis. (silverchair.com)
- Glutamate mediates several modes of neurotransmission in the central nervous system including recently discovered retrograde signaling from neuronal dendrites. (dadospdf.com)
- Neuronal Glutamate Transporters Control Dopaminergic Signaling and Compulsive Behaviors. (albany.edu)
EAAT2
- The family of glutamate transporters is composed of two primary subclasses: the excitatory amino acid transporter (EAAT) family and vesicular glutamate transporter (VGLUT) family. (wikipedia.org)
- Tocris offers the following scientific literature for Glutamate (EAAT) Transporters to showcase our products. (tocris.com)
Activity of glutamate2
- Without the activity of glutamate transporters, glutamate would build up and kill cells in a process called excitotoxicity, in which excessive amounts of glutamate acts as a toxin to neurons by triggering a number of biochemical cascades. (wikipedia.org)
- The activity of glutamate transporters also allows glutamate to be recycled for repeated release. (wikipedia.org)
GABA7
- It has been less clear whether changes in vesicle filling with classical transmitters such as acetylcholine, GABA and glutamate make a difference in the postsynaptic response. (johnshopkins.edu)
- they control ion homeostasis in the CNS interstitium and are indispensable for turnover of major neurotransmitters, such as glutamate, GABA and adenosine. (nature.com)
- Effects of isoflurane and propofol on glutamate and GABA transporters in isolated cortical nerve terminals. (cornell.edu)
- BACKGROUND: Depression of glutamate-mediated excitatory transmission and potentiation of gamma-aminobutyric acid (GABA)-mediated inhibitory transmission appear to be primary mechanisms by which general anesthetics produce anesthesia. (cornell.edu)
- Since effects on transmitter transport have been implicated in anesthetic actions, the authors examined the sensitivity of presynaptic glutamate and GABA transporters to the effects of a representative volatile (isoflurane) and a representative intravenous (propofol) anesthetic. (cornell.edu)
- however, it has also been shown that high doses of modafinil can affect several other neurotransmitter pathways (that are also involved in addictive behaviors such as glutamate, GABA serotonin, and orexin) by unknown mechanisms ( Minzenberg and Carter, 2008 ). (nature.com)
- Current knowledge of Slc6a1 -related disorders: GABA transporter (GAT1) mediated disorders. (albany.edu)
VGluT22
- The role of this unconventional transporter (VGluT3) still remains unknown but, at the moment, has been demonstrated that, in auditory system, the VGluT3 is involved in fast excitatory glutamatergic transmission very similar to the other two vesicular glutamate transporters, VGluT1 and VGluT2. (wikipedia.org)
- Thalamic afferent terminals are preferentially labeled by an isoform of the vesicular glutamate transporter, VGluT2. (nyu.edu)
Neurons7
- In the brain, EAATs remove glutamate from the synaptic cleft and extrasynaptic sites via glutamate reuptake into glial cells and neurons, while VGLUTs move glutamate from the cell cytoplasm into synaptic vesicles. (wikipedia.org)
- Neurons are able to express VGluT3 when they use a neurotransmitter different to Glutamate, for example in the specific case of central 5-HT neurons. (wikipedia.org)
- Here, we investigated the signaling pathways activated in response to the energetic stress created by transient glutamate excitation in cerebellar granule neurons. (jneurosci.org)
- We characterized a glucose dependent hyperpolarization of the mitochondrial membrane potential (Δψ m ) in the majority of neurons after transient glutamate excitation. (jneurosci.org)
- Furthermore, gene silencing of GLUT3 eradicated the increase in Δψ m associated with transient glutamate excitation and potently sensitized neurons to excitotoxicity. (jneurosci.org)
- We have previously identified the system N transporter SN1 as being responsible for glutamine efflux from astroglia and proposed a system A transporter (SAT) in subsequent transport of glutamine into neurons for neurotransmitter regeneration. (dadospdf.com)
- and densely packed hyperchronic hippocampal neurons with altered glutamate receptors and transporters. (educate-yourself.org)
Excitatory amino acid transp3
- Glutamate transporters , also known as excitatory amino acid transporters (EAATs), are sodium- and potassium-dependent members of the solute carrier family 6 (SLC1), widely distributed throughout the brain. (tocris.com)
- 1,2 Five glutamate transporters have been characterized to date: excitatory amino acid transporters 1-5 (EAAT1-5). (silverchair.com)
- Excitatory amino acid transporters (EAATs) on the plasma membrane regulate and modulate glutamate neurotransmission by transporting synaptically released glutamate back into cells. (drexel.edu)
Extracellular space4
- These transporters play the important role of regulating concentrations of glutamate in the extracellular space by transporting it along with other ions across cellular membranes. (wikipedia.org)
- After glutamate is released as the result of an action potential, glutamate transporters quickly remove it from the extracellular space to keep its levels low, thereby terminating the synaptic transmission. (wikipedia.org)
- Extracellular levels of the excitatory neurotransmitter glutamate in the nervous system are maintained by transporters that actively remove glutamate from the extracellular space. (bioseek.eu)
- Glutamate transporters play an important role in removing glutamate from extracellular space into cells. (silverchair.com)
Metabotropic glutamate1
- In addition, group II metabotropic glutamate receptors (mGlu2/3R) have been suggested as a new therapeutic target for drug addiction. (nature.com)
Aspartate5
- Glutamate transporters also transport aspartate and are present in virtually all peripheral tissues, including the heart, liver, testes, and bone. (wikipedia.org)
- They exhibit stereoselectivity for L-glutamate but transport both L-aspartate and D-aspartate. (wikipedia.org)
- Three types of vesicular glutamate transporters are known, VGLUTs 1-3 (SLC17A7, SLC17A6, and SLC17A8 respectively) and the novel glutamate/aspartate transporter sialin. (wikipedia.org)
- Sodium and aspartate symporter Glt Ph is an archaeal homolog of human glutamate transporters, which clear the neurotransmitter glutamate from the synaptic cleft following rounds of neurotransmission ( Danbolt, 2001 ). (elifesciences.org)
- Briefly, the transporters are homotrimers with each protomer consisting of a centrally located scaffold or trimerization domain and a peripheral transport domain that harbors the L-aspartate (L-asp) and three sodium (Na + ) ions binding sites. (elifesciences.org)
Glutamatergic3
- Glutamate transporters are essential players in glutamatergic neurotransmission in the brain, where they maintain extracellular glutamate below cytotoxic levels and allow for rounds of transmission. (elifesciences.org)
- Glutamate is the major excitatory neurotransmitter in the brain, with up to 40% of all synapses being glutamatergic. (unisr.it)
- We hypothesize that glutamate transporter downregulation by neuroleptics increases glutamatergic action at the postsynaptic neuron and thereby may be related to beneficial antipsychotic effects and side effects. (cshl.edu)
Astrocytic2
- The decreased expression of the transporter correlates with its reduced functionality in mouse LRRK2 G2019S purified astrocytic terminals and in Xenopus laevis oocytes expressing human LRRK2 G2019S. (unige.it)
- Homozygous mice deficient in GLT-1, a widely distributed astrocytic glutamate transporter, show lethal spontaneous seizures and increased susceptibility to acute cortical injury. (bioseek.eu)
Plasma membrane2
- The cystine-glutamate antiporter (xCT) is localised to the plasma membrane of cells whilst vesicular glutamate transporters (VGLUTs) are found in the membrane of glutamate-containing synaptic vesicles. (wikipedia.org)
- Mechanistically, we report that pathogenic LRRK2 kinase activity delays the recycling of the transporter to the plasma membrane via Rabs inactivation, causing its intracellular re-localization and degradation. (unige.it)
Vesicular glutamate2
- VGluT3 (Vesicular Glutamate Transporter 3) that is encoded by the SLC17A8 gene is a member of the vesicular glutamate transporter family that transports glutamate into the cells. (wikipedia.org)
- Vesicular glutamate transporters (VGLUTs) allow accumulation of glutamate into synaptic vesicles, as well as secretory vesicles in endocrine tissues. (guidetopharmacology.org)
Receptors and transporters1
- The work in the Gouaux Lab is concentrated on developing molecular mechanisms for the function of receptors and transporters at chemical synapses by utilizing cryo-electron microscopy, x-ray crystallography, and electrophysiology. (ohsu.edu)
Metabolism1
- Functions of glutamate transporters include regulation of excitatory neurotransmission , maintenance of low ambient extracellular glutamate concentrations (protects against neurotoxicity) and providing glutamate for metabolism through the glutamate-glutamine cycle. (tocris.com)
Neurotransmitter glutamate1
- In summary, we demonstrate that SAT2 maintains a key metabolic glutamine/glutamate balance underpinning retrograde signaling by dendritic release of the neurotransmitter glutamate. (dadospdf.com)
Major excitatory neurotransmitter1
- GLUTAMATE is a major excitatory neurotransmitter. (silverchair.com)
High-affinity3
- Na+-dependent transporters have also been called 'high-affinity glutamate transporters', though their glutamate affinity actually varies widely. (wikipedia.org)
- These transmitters are generally released in close apposition to postsynaptic receptors, many of which are ionotropic and have a high affinity for ligand (such as NMDA receptors for glutamate). (johnshopkins.edu)
- Remarkably, a single vesicle filled with glutamate fails to saturate lowaffinity AMPA receptors as well as high-affinity NMDA receptors (123, 132). (johnshopkins.edu)
EAAT33
- The authors studied the effects of volatile anesthetics on one type of glutamate transporters, excitatory amino acid transporter type 3 (EAAT3), and the role of protein kinase C in mediating these effects. (silverchair.com)
- Excitatory amino acid transporter type 3 was expressed in Xenopus oocytes by injection of EAAT3 mRNA. (silverchair.com)
- 0.05) of EAAT3 for glutamate compared with control. (silverchair.com)
Synapses1
- Glutamate signaling occurs at a majority of synapses in the brain and is therefore intrinsic to complex higher brain functions, including cognition and learning. (dadospdf.com)
Vitro2
- Upon electrical stimulation in vivo and depolarization in vitro, glutamine is readily converted to glutamate in activated dendritic subsegments, suggesting that glutamine sustains release of the excitatory neurotransmitter via exocytosis from dendrites. (dadospdf.com)
- Here, we report that Ipt remarkably protects cells against neurotoxin-induced glutamate transporter dysfunction in in vitro and in vivo models. (arizona.edu)
EAATs6
- The EAATs are membrane-bound secondary transporters that superficially resemble ion channels. (wikipedia.org)
- There are two general classes of glutamate transporters, those that are dependent on an electrochemical gradient of sodium ions (the EAATs) and those that are not (VGLUTs and xCT). (wikipedia.org)
- EAATs are antiporters which carry one molecule of glutamate in along with three Na+ and one H+, while export one K+. (wikipedia.org)
- When glutamate is taken up into glial cells by the EAATs, it is converted to glutamine and subsequently transported back into the presynaptic neuron, converted back into glutamate, and taken up into synaptic vesicles by action of the VGLUTs. (wikipedia.org)
- VGLUTs have only between one hundredth and one thousandth the affinity for glutamate that EAATs have. (wikipedia.org)
- The main goals of my research are twofold: to investigate the regulation of EAATs in physiological states and neurological disorders, and to progress the development of compounds that target these transporters for therapeutic purposes. (drexel.edu)
Concentrations1
- L-Glutamate-induced responses were increased gradually with the increased concentrations of isoflurane, a volatile anesthetic. (silverchair.com)
Regulation1
- Our projects include basic research programs to further our knowledge of glutamate transporters regulation in physiological and disease states, and translational projects involving the development of small molecule allosteric modulators of these transporters. (drexel.edu)
Presynaptic1
- Increased cytosolic glutamate in the presynaptic terminal also increases quantal size at the calyx of Held in the auditory pathway (99), prov iding additional evidence against receptor saturation. (johnshopkins.edu)
Astrocytes2
- Mitochondria have limited co-localization with the glutamate transporter GLT-1 in primary astrocytes in culture. (brad.ac.uk)
- Estimating the glutamate transporter surface density in distinct sub-cellular compartments of mouse hippocampal astrocytes. (albany.edu)
Gene1
- Post-mortem studies in schizophrenic patients revealed alterations in glutamate transporter gene expression. (cshl.edu)
Membrane4
- Glutamate transporters are a family of neurotransmitter transporter proteins that move glutamate - the principal excitatory neurotransmitter - across a membrane. (wikipedia.org)
- Mitochondria also possess mechanisms for taking up glutamate that are quite distinct from membrane glutamate transporters. (wikipedia.org)
- Integral membrane glutamate transporters couple the concentrative substrate transport to ion gradients. (biorxiv.org)
- Using two-electrode voltage clamp, membrane currents were recorded before, during, and after application of L-glutamate. (silverchair.com)
Kinase3
- Glutamate excitation induced a rapid alteration in the AMP:ATP ratio that was associated with the activation of the AMP-activated protein kinase (AMPK). (jneurosci.org)
- Notably, inhibition of the CaMKK (calmodulin-dependent protein kinase kinase) had little affect on GLUT translocation, whereas the inhibition or knockdown of AMPK (compound C, siRNA) activity prevented GLUT3 translocation to the cell surface after glutamate excitation. (jneurosci.org)
- Oocytes pretreated with any of the three protein kinase C inhibitors alone (chelerythrine, staurosporine, or calphostin C) did not affect basal transporter current. (silverchair.com)
Archaeal1
- Recent studies have revealed transport rate heterogeneity in an archaeal glutamate transporter homologue Glt Ph , inconsistent with simple kinetic models. (biorxiv.org)
Subtypes1
- Arriza et al (1994) Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex. (tocris.com)
Proteins2
- In LRRK2 G2019S knock-in mouse brain, the correct surface localization of the endogenous transporter is impaired, resulting in its interaction with a plethora of endo-vesicular proteins. (unige.it)
- Research in the A. Mortensen lab focuses on understanding mechanisms that regulate glutamate transporters, crucial proteins in the central nervous system (CNS) that modulate excitatory transmission. (drexel.edu)