Release glutamate transporters excitatory amino acid transporter 4. Medical search. Frequent questions

Extracellular excitatory amino acids are mainly transported into cells by excitatory amino acid transporters (EAATs) expressed on astrocytes to avoid excessive excitation of neurons. (spandidos-publications.com)
Finally, the cross-talk between glutamate and microglia/astrocytes could involve a positive feedback loop that accelerates excitotoxicity. (springer.com)
3 , 4 Astrocytopathy is a central element of neurological disorders and, depending on the disease context, astrocytes undergo complex changes, which vary from astroglial atrophy with loss of function, to pathological remodelling or reactivity and may develop alone or in combination. (nature.com)
constriction was attributed to PLA2-mediated arachidonic acid production by astrocytes, followed by diffusion of the arachidonic acid to smooth muscle and subsequent metabolism by cytochrome P450 4A (ω-hydroxylase) to 20-hydroxyeicosatetraenoic acid (20-HETE). (biomedcentral.com)
Following neurotransmission, astrocytes remove excess extracellular glutamate to prevent neurotoxicity. (eneuro.org)
Primary cultures of wild-type mouse astrocytes expressed S1P 1,2,3 transcripts, and selective deletion of S1P 1 and/or S1P 3 in cerebral cortical astrocytes, did not alter S1P-mediated, dose-dependent inhibition of glutamate uptake. (eneuro.org)
Pharmacological antagonists, S1P 2 -null astrocytes, and Gα 12 hemizygous-null astrocytes indicated that S1P 2 -Gα 12 -Rho/ROCK signaling was primarily responsible for the S1P-dependent inhibition of glutamate uptake. (eneuro.org)
In addition, S1P exposure increased mitochondrial oxygen consumption rates (OCRs) in wild-type astrocytes and reduced OCRs in S1P 2 -null astrocytes, implicating receptor selective metabolic consequences of S1P-mediated glutamate uptake inhibition. (eneuro.org)
Astrocytes are major producers of GSH, and they transport GSH to neurons via specific transporters, such as the excitatory amino acid transporter 2 (EAAT2) and the system xc- cystine/glutamate antiporter. (cellg8.com)
Hence, it is of great significance to reveal the mechanism behind drug addiction, and thanks to the advancing technology in the neuroscience, accumulating studies help people understand how versatile astrocytes work in drug addiction indeed [ 4 ]. (degruyter.com)
[4] Apolipoprotein E transports cholesterol from astrocytes to neurons and other glial cells, regulating cell signaling in the brain. (atozwiki.com)
[4] Astrocytes in humans are more than twenty times larger than in rodent brains, and make contact with more than ten times the number of synapses. (atozwiki.com)
Research since the mid-1990s has shown that astrocytes propagate intercellular Ca 2+ waves over long distances in response to stimulation, and, similar to neurons, release transmitters (called gliotransmitters ) in a Ca 2+ -dependent manner. (atozwiki.com)
[6] Data suggest that astrocytes also signal to neurons through Ca 2+ -dependent release of glutamate . (atozwiki.com)

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)
Excitatory amino acid transporters (EAATs) on the plasma membrane regulate and modulate glutamate neurotransmission by transporting synaptically released glutamate back into cells. (drexel.edu)
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)
Excitatory amino acid transporters (EAATs) of the solute carrier family 1A (SLC1A) take up the neurotransmitter L-glutamate from the synaptic environment, which is necessary to keep the extracellular concentration low and prevent neurotoxicity 1 , 2 . (nature.com)

EAAT1-2 are glial, EAAT3-4 are neuronal, and the mRNA of EAAT5 is distributed in the neurons and glia of retina. (silverchair.com)
A study has shown that neurons in the ischemic penumbra may undergo apoptosis hours or days after ischemia and alleviating ischemia reperfusion injury is an achievable therapeutic goal in the early intervention of ischemic stroke aimed at limiting the amount of infarction ( 4 ). (spandidos-publications.com)
Anti-GAD65 antibody (Ab) acts on the terminals of inhibitory neurons that suppress GABA release, whereas anti-VGCC, anti-mGluR1, and anti-GluR Abs impair LTD induction. (springer.com)
First, since chained inhibitory neurons shape the output signals through the mechanism of disinhibition/inhibition, impairments of GABA release and LTD distort the conversion process from the "internal model" to the output signals. (springer.com)
Horizontal cell actions are in turn tuned by neuromodulators released by other retinal neurons. (org.es)
However, later intracellular marking techniques, in which dyes were injected from the electrode tips into the cytoplasm of the recorded neuron, revealed that horizontal cells, second order neurons postsynaptic to cones, were the source of the S-potentials (3, 4). (org.es)
We are specifically focusing on two groups of transporters vesicular neurotransmitter transporters that package neurotransmitters into vesicles for release, and glutamine transporters that shuttle glutamine, a precursor for two major neurotransmitters glutamate and GABA, to neurons from glia, the supporting cells that surround them. (stanford.edu)
Though glutamate is present in all neurons, only a few are glutamatergic, releasing glutamate as their neurotransmitter. (org.es)
Using immunocytochemical techniques, neurons containing glutamate are identified and labeled with a glutamate antibody. (org.es)
These neurons are believed to release GABA, not glutamate, as their neurotransmitter (Yazulla, 1986), suggesting the weak glutamate labeling reflects the pool of metabolic glutamate used in the synthesis of GABA. (org.es)
Glutamate incorporated into Muller cells is rapidly broken down into glutamine, which is then exported from glial cells and incorporated into surrounding neurons (Pow and Crook, 1996). (org.es)
Many structures and processes are involved in the development of a seizure, including neurons, ion channels, receptors, glia, and inhibitory and excitatory synapses. (medscape.com)

Volatile anesthetics (VAs) have been demonstrated to enhance the uptake of glutamate in in vitro systems. (silverchair.com)
EAAT2 accounts for 80-90% of this activity of extracellular excitatory amino acid uptake ( 7 ). (spandidos-publications.com)
Potent competitive inhibitor of L-glutamate uptake. (tocris.com)
Glutamate uptake is reduced in prefrontal cortex in Huntington's disease. (neurotree.org)
Here, S1P receptor knock-out mice, primary astrocyte cultures, and receptor-selective chemical tools were used to examine the effects of S1P on glutamate uptake. (eneuro.org)
S1P inhibited astrocytic glutamate uptake in a dose-dependent manner and increased mitochondrial oxygen consumption, primarily through S1P 2 . (eneuro.org)
Extracellular glutamate is excitotoxic and its levels are controlled by astrocyte uptake. (eneuro.org)
Here, we show that astrocytic S1P 2 activation by S1P results in glutamate uptake inhibition to promote excitotoxic damage. (eneuro.org)
S1P receptor modulators, including approved drugs for treating MS, e.g., fingolimod (FTY720) and siponimod (BAF312), do not engage S1P 2 , thus avoiding glutamate uptake inhibition. (eneuro.org)
The involvement of glutamate dysregulation in these neurologic diseases makes pharmacological modulation of glutamate uptake an attractive therapeutic target ( Anderson and Swanson, 2000 ). (eneuro.org)
It is well-established that the secondary active transporters Glt Tk and Glt Ph catalyze coupled uptake of aspartate and three sodium ions, but insight in the kinetic mechanism of transport is fragmentary. (nature.com)

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)
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)

EAAT4 is expressed predominantly in the cerebellum, has high affinity for the excitatory amino acids L-aspartate and L-glutamate. (wikipedia.org)
Combined with previous pre-equilibrium binding studies, a full kinetic mechanism of structurally characterized aspartate transporters of the SLC1A family is now emerging. (nature.com)
Linkage and association of the mitochondrial aspartate/glutamate carrier SLC25A12 gene with autism. (neurotransmitter.net)
Two single nucleotide polymorphisms (SNPs) that showed evidence for divergent distribution between autistic and nonautistic subjects were identified, both within SLC25A12, a gene encoding the mitochondrial aspartate/glutamate carrier (AGC1). (neurotransmitter.net)
This transporter also transports aspartate, and mutations in this gene are thought to cause dicarboxylicamino aciduria, also known as glutamate-aspartate transport defect. (abbkine.com)
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)

GAD65 is involved in the synthesis, packaging, and release of GABA, whereas the other three play important roles in the induction of long-term depression (LTD). Thus, the auto-antibodies toward these synaptic molecules likely impair fundamental synaptic machineries involved in unique functions of the cerebellum, potentially leading to the development of cerebellar ataxias (CAs). (springer.com)
Among these diverse features, it should be acknowledged that auto-antibodies toward glutamate receptors, GABA receptors, and K + channel-related proteins are preferentially found in autoimmune limbic encephalitis but not in IMCAs [ 10 ] (Table 1 ). (springer.com)
they control ion homeostasis in the CNS interstitium and are indispensable for turnover of major neurotransmitters, such as glutamate, GABA and adenosine. (nature.com)
This has been supported by the results from double-labeling studies using antibodies to both GABA and glutamate: glutamate-positive amacrine cells also label with the GABA antibodies (Jojich and Pourcho, 1996, Yang, 1996). (org.es)
The main groups include sodium channel blockers, calcium current inhibitors, gamma-aminobutyric acid (GABA) enhancers, glutamate blockers, carbonic anhydrase inhibitors, hormones, and drugs with unknown mechanisms of action (see the image below). (medscape.com)

This Human Excitatory amino acid transporter 3 (SLC1A1) ELISA Kit employs a two-site sandwich ELISA to quantitate SLC1A1 in samples. (abbkine.com)
Human Excitatory amino acid transporter 3 (SLC1A1) ELISA Kit has high sensitivity and excellent specificity for detection of Human SLC1A1. (abbkine.com)

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)
In our studies on neurotransmitter metabolism we have focused our efforts on transporters, a functional class of proteins that move neurotransmitters and other small molecules across membranes in cells. (stanford.edu)
L-Aspartic acid is used as a cell culture media component for the commercial biomanufacture of therapeutic recombinant proteins and monoclonal antibodies. (sigmaaldrich.com)
It has been shown that more than 99% of blood BDNF proteins are stored in platelets and that these proteins can be released into the serum [ 6 ] through pharmacological treatment [ 15 , 16 ]. (hindawi.com)

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)
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 incorporated into these cell types through a high affinity glutamate transporter located in the plasma membrane. (org.es)
SLC1A1 encodes a member of the high-affinity glutamate transporters that play an essential role in transporting glutamate across plasma membranes. (abbkine.com)

Secondary effects of brain trauma can be reduced by molecules that limit glutamate release, antagonists of ionotropic glutamate receptors, and compounds that target calcium influx. (drexel.edu)
It was hypothesized that the activation of xc- prevents drug seeking by increasing glutamatergic tone on presynaptic group II metabotropic glutamate receptors (mGluR2/3) and thereby inhibiting excitatory transmission. (jneurosci.org)
Glutamate and glutamate receptors in the vertebrate retina. (org.es)
Once released, the neurotransmitter diffuses across the cleft and binds to receptors on the postsynaptic cell, allowing the signal to propagate. (org.es)
2) Specific neurotransmitter receptors are localized on the postsynaptic cells, and (3) there exists a mechanism to stop neurotransmitter release and clear molecules from the cleft. (org.es)
Neuroactive glutamate is classified as an excitatory amino acid (EAA) because glutamate binding onto postsynaptic receptors typically stimulates, or depolarizes, the postsynaptic cells. (org.es)

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)
Brain-derived neurotrophic factor (BDNF) contributes to brain development [ 1 , 2 ] and is related to neuronal survival and activity since it acts as a modulator of neurotransmitter levels and participates in neuronal plasticity [ 3 , 4 ]. (hindawi.com)

In brain, these transporters are crucial in terminating the postsynaptic action of the neurotransmitter glutamate, and in maintaining extracellular glutamate concentrations below neurotoxic levels. (abbkine.com)

The autoantigens include glutamic acid decarboxylase 65 (GAD65), voltage-gated Ca 2+ channel (VGCC), metabotropic glutamate receptor type 1 (mGluR1), and glutamate receptor delta (GluRdelta). (springer.com)

Dynamic target of seizure control in management of epilepsy is achieving balance between factors that influence excitatory postsynaptic potential (EPSP) and those that influence inhibitory postsynaptic potential (IPSP). (medscape.com)

Transporters have many characteristics that make them excellent pharmacological targets, and not surprisingly some of the most effective treatments for neuropsychiatric disorders are directed at transporters. (stanford.edu)
Although the source of circulating BDNF is uncertain, it is stored in platelets and can be released through pharmacological treatment. (hindawi.com)

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)

Glutamate transporters play an important role in removing glutamate from extracellular space into cells. (silverchair.com)

Arriza et al (1994) Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex. (tocris.com)
1994). Though Muller cells take up glutamate, they do not label with glutamate antibodies (Jojich and Pourcho, 1996). (org.es)
Obtuve el título de doctor en junio de 1994, obteniendo el premio extraordinario de doctorado. (unav.edu)
Desde que defendí mi tesis doctoral en el año 1994, mi labor investigadora que he desarrollado ha sido en el campo de la enfermedad de Alzheimer. (unav.edu)

A metabolomic study of brain tissues from aged mice with low expression of the vesicular monoamine transporter 2 (VMAT2) gene. (neurotree.org)
Differential gene expression in the striatum of mice with very low expression of the vesicular monoamine transporter type 2 gene. (neurotree.org)
Glutamate is incorporated into the vesicles by a glutamate transporter located in the vesicular membrane. (org.es)

1,2 Five glutamate transporters have been characterized to date: excitatory amino acid transporters 1-5 (EAAT1-5). (silverchair.com)

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)

Glutamate transporters play an important role in maintaining extracellular glutamate homeostasis. (silverchair.com)
however, a clear link between glutamate homeostasis and S1P signaling has not been established. (eneuro.org)

Glutamate neurotoxicity has been reported in multiple neurologic diseases including multiple sclerosis (MS), representing a shared neurodegenerative mechanism. (eneuro.org)
Astrocytic S1P-S1P 2 signaling increased extracellular glutamate, which could contribute to neurotoxicity. (eneuro.org)
Development and use of S1P 2 -selective antagonists may provide a new approach to reduce glutamate neurotoxicity in neurologic diseases. (eneuro.org)
S1P 2 antagonists may provide a means to reduce S1P-induced glutamate neurotoxicity and ameliorate neurologic diseases. (eneuro.org)

L-Glutamate-induced responses were increased gradually with the increased concentrations of isoflurane, a volatile anesthetic. (silverchair.com)
The direct action of riluzole evoking BDNF release from human platelets at therapeutic concentrations is important and may contribute to the understanding of its mechanisms of action in the treatment of depression. (hindawi.com)

Neuroactive glutamate is stored in synaptic vesicles in presynaptic axon terminals (Fykse and Fonnum, 1996). (org.es)

Hohnholt MC, Dringen R. Effects of glutathione depletion and inhibition of glutathione synthesis on the hypotaurine- and taurine-modulated release of dopamine from cultured PC12 cells. (cellg8.com)

Glutathione (GSH) is a tripeptide molecule composed of cysteine, glutamate, and glycine that plays a critical role in regulating redox balance in the brain. (cellg8.com)
Neurotransmitter compounds can be small molecules, such as glutamate and glycine, or large peptides, such as vasoactive intestinal peptide (VIP). (org.es)

In isolated retinas, vasodilations dependent on astrocyte metabolism of arachidonic acid by cytochrome (CYP) P450 2C11 (epoxygenase) to epoxyeicosatrienoic acids (EETs) became less likely as NO levels increased and directly inhibited epoxygenase activity [ 5 ]. (biomedcentral.com)
GSH synthesis and recycling are regulated by a variety of factors, including oxidative stress, cytokines, and growth factors, which can modulate the expression and activity of key enzymes involved in GSH metabolism, such as gamma-glutamylcysteine synthetase (γ-GCS) and glutathione peroxidase 4 (GPx4). (cellg8.com)
Glucose is the major substrate for ATP synthesis through glycolysis and oxidative phosphorylation (OXPHOS), whereas intermediary metabolism through the tricarboxylic acid (TCA) cycle utilizes non-glucose-derived monocarboxylates, amino acids, and alpha ketoacids to support mitochondrial ATP and GTP synthesis. (molvis.org)
Confocal studies showed differential cellular and compartmental distribution of isozymes involved in glucose, glutamate, glutamine, lactate, and creatine metabolism. (molvis.org)

When ischemic stroke occurs, cerebral ischemia and hypoxia cause the release of excessive excitatory amino acids, mainly glutamic acid and aspartic acid, which exert excitotoxic effects on the central nervous system. (spandidos-publications.com)
L-Aspartic acid is a non-essential amino acid. (sigmaaldrich.com)

An increased PC activity upon ammonia exposure and the importance of PC activity for glutamine synthesis has previously been demonstrated while the importance of GDH for generation of glutamate as precursor for glutamine synthesis has received little attention. (123dok.net)

Excitatory amino-acid transporter 4 (EAAT4) is a protein that in humans is encoded by the SLC1A6 gene. (wikipedia.org)
These diseases are the result of a defect in transport of sialic acid across lysosomal membranes and are associated with mutations in the gene encoding the sialic acid transporter sialin. (stanford.edu)
Negative association findings and research involving the serotonin transporter gene, FMR1, RELN, WNT2, HOXA1, and HOXB1 genes may be found elsewhere on this site . (neurotransmitter.net)

When stimulated by these amino acids, EAAT4 conducts chloride ions. (wikipedia.org)

This requires a continuous de novo synthesis of glutamate, likely involving the action of both pyruvate carboxylase (PC) and glutamate dehydrogenase (GDH). (123dok.net)

This has a profound impact on the level of receptor activation and excitatory transmission. (drexel.edu)

Restoring extracellular glutamate with systemic administration of cysteine prodrugs prevented the reinstatement of cocaine seeking. (jneurosci.org)
Therefore, a mechanism that may account for the ameliorative effect of cysteine prodrugs on cocaine seeking is that the increase in extracellular glutamate produced by activating xc- restores tone on presynaptic mGluR2/3 and thereby reduces synaptic glutamate release. (jneurosci.org)

Glutamate (Fig. 1) is believed to be the major excitatory neurotransmitter in the retina. (org.es)

In the first experiment, the capacity of glutamate derived from xc- to regulate excitatory transmission via mGluR2/3 was determined. (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)

Some horizontal and/or amacrine cells can also display weak labeling with glutamate antibodies (Ehinger et al. (org.es)

The transport domains are mobile and move through the lipid bilayer (alike an elevator) when translocating the amino acid substrate and co-transported ions across the membrane 13 . (nature.com)
The structures show that both substrate translocation and release involve movements of the bulky transport domain through the lipid bilayer. (elifesciences.org)

Two experiments were conducted to examine the hypothesis that glutamate derived from xc- stimulates inhibitory presynaptic mGluR2/3, thereby reducing synaptic glutamate release and preventing cocaine-primed drug seeking. (jneurosci.org)

Sodium salt of 7-Chlorokynurenic acid (Cat. (tocris.com)
This transporter selectively accumulates glutamate through a sodium-independent, ATP-dependent process (Naito and Ueda, 1983, Tabb and Ueda, 1991, Fykse and Fonnum, 1996), resulting in a high concentration of glutamate in each vesicle. (org.es)

Using two-electrode voltage clamp, membrane currents were recorded before, during, and after application of L-glutamate. (silverchair.com)
To overcome the complication that purified transporters may adopt right-side-out or inside-out membrane orientations upon reconstitution, thereby confounding the kinetic analysis, we employed a rapid method using synthetic nanobodies to inactivate one population. (nature.com)
Thus, glutamate gradients of a million-fold across the membrane under resting conditions can be sustained. (nature.com)

So, according to numerous studies, not only ACh (which by the way does not always lead to a contraction of the muscle fiber) is released in the vertebrate neuromuscular synapse, but also a number of other synaptically active molecules. (intechopen.com)

Some neuroactive compounds are amino acids, which also have metabolic functions in the presynaptic cell. (org.es)

Neurotransmitter molecules can also bind onto presynaptic autoreceptors and transporters, regulating subsequent release and clearing excess neurotransmitter from the cleft. (org.es)
Among the drugs proposed is riluzole (2-amino-6-trifluoromethoxy benzothiazole), which was originally developed as an anticonvulsant [ 29 ] but has been used in a number of trials for psychiatric conditions in which glutamate excess has been proposed as part of the pathologic mechanism [ 30 - 33 ]. (hindawi.com)

And these molecules can be released from both nerve terminal (anterograde signal), and from muscle fiber (retrograde signal). (intechopen.com)

When the presynaptic neuron is stimulated, calcium channels open and the influx of calcium ions into the axon terminal triggers a cascade of events leading to the release of neurotransmitter. (org.es)

Anatomy2

Organisms1

Chemicals and Drugs32

Phenomena and Processes1

Astrocytes14

EAATs4

Neurons12

Uptake11

EAAT23

Aspartate7

GABA5

Human excitatory2

Proteins4

Neurotransmission2

High affinity2

Receptors6

Neuronal2

Neurotransmitter glutamate1

Metabotropic1

Postsynaptic1

Pharmacological2

EAAT33

Extracellular space1

19944

Vesicular3

EAAT11

Modulators1

Homeostasis2

Neurotoxicity4

Concentrations2

Synaptic vesicles1

Inhibition1

Glycine2

Metabolism4

Aspartic acid2

Glutamine1

Gene3

EAAT41

Dehydrogenase1

Receptor1

Cysteine2

Retina1

Regulate1

Basal1

Antibodies1

Lipid bilayer2

Inhibitory1

Sodium2

Membrane3

Synaptically1

Compounds1

Excess2

Molecules1

Presynaptic1