Sun . 20 Jul 2020
TR | RU | UK | KK | BE |

Glutamate receptor

glutamate receptors, glutamate receptor antagonists
Glutamate receptors are synaptic receptors located primarily on the membranes of neuronal cells Glutamate the conjugate base of glutamic acid is abundant in the human body, but particularly in the nervous system and especially prominent in the human brain where it is the body's most prominent neurotransmitter, the brain's main excitatory neurotransmitter, and also the precursor for GABA, the brain's main inhibitory neurotransmitter1 Glutamate receptors are responsible for the glutamate-mediated postsynaptic excitation of neural cells, and are important for neural communication, memory formation, learning, and regulation

Glutamate receptors are implicated in a number of neurological conditions Their central role in excitotoxicity and prevalence in the central nervous system has been linked or speculated to be linked to many neurodegenerative diseases, and several other conditions have been further linked to glutamate receptor gene mutations or receptor autoantigen/antibody activity

Contents

  • 1 Function
    • 11 Glutamate
    • 12 Glutamate receptors
  • 2 Types
    • 21 Ionotropic
    • 22 Metabotropic
  • 3 Structure, mechanism and function
    • 31 Ionotropic
    • 32 Metabotropic
    • 33 Outside the central nervous system
  • 4 General clinical implications
    • 41 Autoimmunity and antibody interactions with glutamate receptors and their subunit genes
    • 42 Excitotoxicity
    • 43 Neurodegeneration
  • 5 Conditions with demonstrated associations to glutamate receptors
    • 51 Aching
    • 52 Attention deficit hyperactivity disorder ADHD
    • 53 Autism
    • 54 Diabetes
    • 55 Huntington's disease
    • 56 Ischemia
    • 57 Multiple sclerosis
    • 58 Parkinson's disease Parkinsonism
    • 59 Rasmussen's encephalitis
    • 510 Schizophrenia
    • 511 Seizures
  • 6 Other diseases suspected of glutamate receptor link
    • 61 Neurodegenerative diseases with a suspected excitotoxicity link
    • 62 Other
  • 7 See also
  • 8 References
  • 9 External links

Functionedit

Glutamateedit

Main article: Glutamic acid

Glutamate Glutamic acid is the most prominent neurotransmitter in the body, and it is the main excitatory neurotransmitter,1 being present in over 50% of nervous tissue2 Glutamate was initially discovered to be a neurotransmitter in insect studies in the early 1960s

Glutamate is also used by the brain to synthesize GABA γ-Aminobutyric acid, the main inhibitory neurotransmitter of the mammalian central nervous system, which plays a role in regulating neuronal excitability throughout the nervous system and is also directly responsible for the regulation of muscle tone in humans13

Glutamate receptorsedit

Mammalian glutamate receptors are classified based on their pharmacology However, glutamate receptors in other organisms have different pharmacology, and therefore these classifications do not hold One of the major functions of glutamate receptors appears to be the modulation of synaptic plasticity, a property of the brain thought to be vital for memory and learning Both metabotropic and ionotropic glutamate receptors have been shown to have an effect on synaptic plasticity4 An increase or decrease in the number of ionotropic glutamate receptors on a postsynaptic cell may lead to long-term potentiation or long-term depression of that cell, respectively567 Additionally, metabotropic glutamate receptors may modulate synaptic plasticity by regulating postsynaptic protein synthesis through second messenger systems8 Research shows that glutamate receptors are present in CNS glial cells as well as neurons9 These glutamate receptors are suggested to play a role in modulating gene expression in glial cells, both during the proliferation and differentiation of glial precursor cells in brain development and in mature glial cells10

Typesedit

Glutamate receptors can be divided into two groups according to the mechanism by which their activation gives rise to a postsynaptic current11 Ionotropic glutamate receptors iGluRs form the ion channel pore that activates when glutamate binds to the receptor Metabotropic glutamate receptors mGluRs indirectly activate ion channels on the plasma membrane through a signaling cascade that involves G proteins Ionotropic receptors tend to be quicker in relaying information, but metabotropic ones are associated with a more prolonged stimulus This is due to the usage of many different messengers to carry out the signal, but since there is a cascade, just one activation of a G-protein can lead to multiple activations Glutamate receptors are usually not specifically geared towards glutamate exclusively as the ligand requires another agonist

Of the many specific subtypes of glutamate receptors, it is customary to refer to primary subtypes by a chemical that binds to it more selectively than glutamate The research, however, is ongoing, as subtypes are identified and chemical affinities measured Several compounds are routinely used in glutamate receptor research and associated with receptor subtypes:

Type Name Agonists
ionotropic NMDA receptor NMDA
Kainate receptor Kainate
AMPA receptor AMPA
metabotropic mGluR L-AP4, ACPD, L-QA12

Due to the diversity of glutamate receptors, their subunits are encoded by numerous gene families Sequence similarities between mammals show a common evolutionary origin for many mGluR and all iGluR genes13 Conservation of reading frames and splice sites of GluR genes between chimpanzees and humans is complete, suggesting no gross structural changes after humans diverged from the human-chimpanzee common ancestor However, there is a possibility that two human-specific "fixed" amino acid substitutions, D71G in GRIN3A and R727H in GRIN3B, are specifically associated with human brain function14

Ionotropicedit

Mammalian ionotropic glutamate receptor subunits and their genes:1516

Mammalian receptor family Subunit

Old nomenclature

Gene Chromosome
human
AMPA GluA1 GluR1 GRIA1 5q33
GluA2 GluR2 GRIA2 4q32-33
GluA3 GluR3 GRIA3 Xq25-26
GluA4 GluR4 GRIA4 11q22-23
Kainate GluK1 GluR5 GRIK1 21q211-221
GluK2 GluR6 GRIK2 6q163-q21
GluK3 GluR7 GRIK3 1p34-p33
GluK4 KA-1 GRIK4 11q223
GluK5 KA-2 GRIK5 19q132
NMDA GluN1NR1 GRIN1 9q343
GluN2A NR2A GRIN2A 16p132
GluN2B NR2B GRIN2B 12p12
GluN2C NR2C GRIN2C 17q24-q25
GluN2D NR2D GRIN2D 19q131qter
GluN3A NR3A GRIN3A 9q311
GluN3B NR3B GRIN3B 19p133

Metabotropicedit

Mammalian metabotropic glutamate receptors are all named mGluR# and are further broken down into three groups:

Group Receptor Gene Chromosome
human
Effect
1 mGluR1 GRM1 6q24 Increase in Ca2+ concentration in the cytoplasm
mGluR5 GRM5 11q143 Release of K+ from the cell by activating K+ ionic channels
2 mGluR2 GRM2 3p212 Inhibition of adenylyl cyclase causing shutdown of the cAMP-dependent pathway
And therefore decreasing amount of cAMP
mGluR3 GRM3 7q211-q212
3 mGluR4 GRM4 6p213 Activation of Ca2+ channels, allowing more Ca2+ to enter the cell17
mGluR6 GRM6 5q35
mGluR7 GRM7 3p26-p25
mGluR8 GRM8 7q313-q321

In other non mammalian organisms, the classification and subunit composition of glutamate receptors is different

Structure, mechanism and functionedit

Glutamate receptors exist primarily in the central nervous system These receptors can be found on the dendrites of postsynaptic cells and bind to glutamate released into the synaptic cleft by presynaptic cells They are also present on both astrocytes and oligodendrocytes10 The glutamate binds to the extracellular portion of the receptor and provokes a response, but the various types of receptors can produce different responses11 Ionotropic and metabotropic glutamate receptors, with the exception of NMDA, are found on cultured glial cells, which can open in response to glutamate and cause cells to activate second messengers to regulate gene expression and release neuroactive compounds9 Furthermore, brain slices show glutamate receptors are ubiquitously expressed in both developing and mature astrocytes and oligodendrocytes in vivo Because of this, glial glutamate receptors are thought to be vital for glial cell development10

Ionotropicedit

Main article: Ionotropic glutamate receptor

Ionotropic glutamate receptors, by definition, are ligand-gated nonselective cation channels that allow the flow of K+, Na+ and sometimes Ca2+ in response to glutamate binding In C elegans and Drosophila, invertebrate-specific subunits enable the flow of negative chloride ions rather than cations Upon binding, the agonist will stimulate direct action of the central pore of the receptor, an ion channel, allowing ion flow and causing excitatory postsynaptic current EPSC This current is depolarizing and, if enough glutamate receptors are activated, may trigger an action potential in the postsynaptic neuron All produce excitatory postsynaptic current, but the speed and duration of the current is different for each type NMDA receptors have an internal binding site for an Mg2+ ion, creating a voltage-dependent block, which is removed by outward flow of positive current18 Since the block must be removed by outward current flow, NMDA receptors rely on the EPSC produced by AMPA receptors to open NMDA receptors are permeable to Ca2+,19 which is an important cation in the nervous system20 and has been linked to gene regulation21 The flow of Ca2+ through NMDA receptors is thought to cause both long-term potentiation LTP, of synapse efficacy and long-term depression LTD by transducing signaling cascades and regulating gene expression

Metabotropicedit

Main article: Metabotropic glutamate receptor

Metabotropic glutamate receptors, which belong to subfamily C of G protein-coupled receptors are divided into three groups, with a total of eight subtypes in mammals; this is not necessarily the case for most organisms The mGluRs are composed of three distinct regions: the extracellular region, the transmembrane region, and the intracellular region22 The extracellular region is composed of a venus flytrap VFT module that binds glutamate,23 and a cysteine-rich domain that is thought to play a role in transmitting the conformational change induced by ligand binding from in the VFT module to the transmembrane region22 The transmembrane region consists of seven transmembrane domains and connects the extracellular region to the intracellular region where G protein coupling occurs23 Glutamate binding to the extracellular region of an mGluR causes G proteins bound to the intracellular region to be phosphorylated, affecting multiple biochemical pathways and ion channels in the cell24 Because of this, mGluRs can both increase or decrease the excitability of the postsynaptic cell, thereby causing a wide range of physiological effects

Outside the central nervous systemedit

Glutamate receptors are thought to be responsible for the reception and transduction of umami taste stimuli Taste receptors of the T1R family, belonging to the same class of GPCR as metabotropic glutamate receptors are involved Additionally, the mGluRs, as well as ionotropic glutamate receptors in neural cells, have been found in taste buds and may contribute to the umami taste25 Numerous ionotropic glutamate receptor subunits are expressed by heart tissue, but their specific function is still unknown Western blots and northern blots confirmed the presence of iGluRs in cardiac tissue Immunohistochemistry localized the iGluRs to cardiac nerve terminals, ganglia, conducting fibers, and some myocardiocytes26 Glutamate receptors are as mentioned above also expressed in pancreatic islet cells27 AMPA iGluRs modulate the secretion of insulin and glucagon in the pancreas, opening the possibility of treatment of diabetes via glutamate receptor antagonists2829 Small unmyelinated sensory nerve terminals in the skin also express NMDA and non-NMDA receptors Subcutaneous injections of receptor blockers in rats successfully analgesized skin from formalin-induced inflammation, raising possibilities of targeting peripheral glutamate receptors in the skin for pain treatment30

General clinical implicationsedit

Specific medical conditions and symptoms are discussed below

Autoimmunity and antibody interactions with glutamate receptors and their subunit genesedit

Various neurological disorders are accompanied by antibody or autoantigen activity associated with glutamate receptors or their subunit genes eg GluR3 in Rasmussen's encephalitis,31 and GluR2 in nonfamilial olivopontocerebellar degeneration32 In 1994 GluR3 was shown to act as an autoantigen in Rasmussen's encephalitis, leading to speculation that autoimmune activity might underlie the condition33 Such findings "suggest" links between glutamate receptors and autoimmune interactions are possible and may be significant in some degenerative diseases,32 however the exact role of such antibodies in disease manifestation is still not entirely known34

Excitotoxicityedit

Overstimulation of glutamate receptors causes neurodegeneration and neuronal damage through a process called excitotoxicity Excessive glutamate, or excitotoxins acting on the same glutamate receptors, overactivate glutamate receptors specifically NMDARs, causing high levels of calcium ions Ca2+ to influx into the postsynaptic cell35

High Ca2+ concentrations activate a cascade of cell degradation processes involving proteases, lipases, nitric oxide synthase, and a number of enzymes that damage cell structures often to the point of cell death36 Ingestion of or exposure to excitotoxins that act on glutamate receptors can induce excitotoxicity and cause toxic effects on the central nervous system37 This becomes a problem for cells, as it feeds into a cycle of positive feedback cell death

Glutamate excitotoxicity triggered by overstimulation of glutamate receptors also contributes to intracellular oxidative stress Proximal glial cells use a cystine/glutamate antiporter xCT to transport cystine into the cell and glutamate out Excessive extracellular glutamate concentrations reverse xCT, so glial cells no longer have enough cystine to synthesize glutathione GSH, an antioxidant38 Lack of GSH leads to more reactive oxygen species ROSs that damage and kill the glial cell, which then cannot reuptake and process extracellular glutamate39 This is another positive feedback in glutamate excitotoxicity In addition, increased Ca2+ concentrations activate nitric oxide synthase NOS and the over-synthesis of nitric oxide NO High NO concentration damages mitochondria, leading to more energy depletion, and adds oxidative stress to the neuron as NO is a ROS40

Neurodegenerationedit

In the case of traumatic brain injury or cerebral ischemia eg, cerebral infarction or hemorrhage, acute neurodegeneration caused by excitotoxicity may spread to proximal neurons through two processes Hypoxia and hypoglycemia trigger bioenergetic failure; mitochondria stop producing ATP energy Na+/K+-ATPase can no longer maintain sodium/potassium ion concentration gradients across the plasma membrane Glutamate transporters EAATs, which use the Na+/K+ gradient, reverse glutamate transport efflux in affected neurons and astrocytes, and depolarization increases downstream synaptic release of glutamate41 In addition, cell death via lysis or apoptosis releases cytoplasmic glutamate outside of the ruptured cell42 These two forms of glutamate release cause a continual domino effect of excitotoxic cell death and further increased extracellular glutamate concentrations

Glutamate receptors' significance in excitotoxicity also links it to many neurogenerative diseases Conditions such as exposure to excitotoxins, old age, congenital predisposition, and brain trauma can trigger glutamate receptor activation and ensuing excitotoxic neurodegeneration This damage to the central nervous system propagates symptoms associated with a number of diseases43

Conditions with demonstrated associations to glutamate receptorsedit

A number of diseases in humans have a proven association with genetic mutations of glutamate receptor genes, or autoantigen/antibody interactions with glutamate receptors or their genes Glutamate receptors and impaired regulation in particular, those resulting in excessive glutamate levels are also one cause of excitotoxicity described above, which itself has been implicated or associated with a number of specific neurodegenerative conditions where neural cell death or degradation within the brain occurs over time3943

Excessive synaptic receptor stimulation by glutamate is directly related to many conditions Magnesium is one of many antagonists at the glutamate receptor, and magnesium deficiencies have demonstrated relationships with many glutamate receptor-related conditions44

Glutamate receptors have been found to have an influence in ischemia/stroke, seizures, Parkinson's disease, Huntington's disease, and aching,45 addiction46 and an association with both ADHD47 and autism48

In most cases these are areas of ongoing research

Achingedit

Hyperalgesia is directly involved with spinal NMDA receptors Administered NMDA antagonists in a clinical setting produce significant side effects, although more research is being done in intrathecal administration37 Since spinal NMDA receptors link the area of pain to the brain's pain processing center, the thalamus, these glutamate receptors are a prime target for treatment One proposed way to cope with the pain is subconsciously through the visualization technique49

Attention deficit hyperactivity disorder ADHDedit

In 2006 the glutamate receptor subunit gene GRIN2B responsible for key functions in memory and learning was associated with ADHD50 This followed earlier studies showing a link between glutamate modulation and hyperactivity 2001,5151 and then between the SLC1A3 solute carrier gene-encoding part of the glutamate transporter process that mapped to a chromosome 5p12 noted in multiple ADHD genome scans52

Further mutations to four different metabotropic glutamate receptor genes were identified in a study of 1013 children with ADHD compared to 4105 controls with non-ADHD, replicated in a subsequent study of 2500 more patients Deletions and duplications affected GRM1, GRM5, GRM7 and GRM8 The study concluded that "CNVs affecting metabotropic glutamate receptor genes were enriched across all cohorts P = 21 × 10−9", "over 200 genes interacting with glutamate receptors were collectively affected by CNVs", "major hubs of the affected genes' network include TNIK50, GNAQ51, and CALM", and "the fact that children with ADHD are more likely to have alterations in these genes reinforces previous evidence that the GRM pathway is important in ADHD"47

A SciBX article in January 2012 commented that "UPenn and MIT teams have independently converged on mGluRs as players in ADHD and autism The findings suggest agonizing mGluRs in patients with ADHD"53

Autismedit

The etiology of autism may include excessive glutamatergic mechanisms In small studies, memantine has been shown to significantly improve language function and social behavior in children with autism5455 Research is underway on the effects of memantine in adults with autism spectrum disorders56

A link between glutamate receptors and autism was also identified via the structural protein ProSAP1 SHANK2 and potentially ProSAP2 SHANK3 The study authors concluded that the study "illustrates the significant role glutamatergic systems play in autism" and "By comparing the data on ProSAP1/Shank2−/− mutants with ProSAP2/Shank3αβ−/− mice, we show that different abnormalities in synaptic glutamate receptor expression can cause alterations in social interactions and communication Accordingly, we propose that appropriate therapies for autism spectrum disorders are to be carefully matched to the underlying synaptopathic phenotype"48

Diabetesedit

Diabetes is a peculiar case because it is influenced by glutamate receptors present outside of the central nervous system, and it also influences glutamate receptors in the central nervous system

Diabetes mellitus, an endocrine disorder, induces cognitive impairment and defects of long-term potential in the hippocampus, interfering with synaptic plasticity Defects of long-term potential in the hippocampus are due to abnormal glutamate receptors, to be specific the malfunctioning NMDA glutamate receptors during early stages of the disease57

Research is being done to address the possibility of using hyperglycemia and insulin to regulate these receptors and restore cognitive functions Pancreatic islets regulating insulin and glucagon levels also express glutamate receptors27 Treating diabetes via glutamate receptor antagonists is possible, but not much research has been done The difficulty of modifying peripheral GluR without having detrimental effects on the central nervous system, which is saturated with GluR, may be the cause of this

Huntington's diseaseedit

In 2004, a specific genotype of human GluR6 was discovered to have a slight influence on the age of onset of Huntington's disease58

In addition to similar mechanisms causing Parkinson's disease with respect to NMDA or AMPA receptors, Huntington's disease was also proposed to exhibit metabolic and mitochondrial deficiency, which exposes striatal neurons to the over activation of NMDA receptors37 Using folic acid has been proposed as a possible treatment for Huntington's due to the inhibition it exhibits on homocysteine, which increases vulnerability of nerve cells to glutamate59 This could decrease the effect glutamate has on glutamate receptors and reduce cell response to a safer level, not reaching excitotoxicity

Ischemiaedit

During ischemia, the brain has been observed to have an unnaturally high concentration of extracellular glutamate60 This is linked to an inadequate supply of ATP, which drives the glutamate transport levels that keep the concentrations of glutamate in balance61 This usually leads to an excessive activation of glutamate receptors, which may lead to neuronal injury After this overexposure, the postsynaptic terminals tend to keep glutamate around for long periods of time, which results in a difficulty in depolarization61 Antagonists for NMDA and AMPA receptors seem to have a large benefit, with more aid the sooner it is administered after onset of the neural ischemia62

Multiple sclerosisedit

Inducing experimental autoimmune encephalomyelitis in animals as a model for multiple sclerosisMS has targeted some glutamate receptors as a pathway for potential therapeutic applications63 This research has found that a group of drugs interact with the NMDA, AMPA, and kainate glutamate receptor to control neurovascular permeability, inflammatory mediator synthesis, and resident glial cell functions including CNS myelination Oligodendrocytes in the CNS myelinate axons; the myelination dysfunction in MS is partly due to the excitotoxicity of those cells By regulating the drugs which interact with those glutamate receptors, regulating glutamate binding may be possible, and thereby reduce the levels of Ca2+ influx The experiments showed improved oligodendrocyte survival, and remyelination increased Furthermore, CNS inflammation, apoptosis, and axonal damage were reduced63

Parkinson's disease Parkinsonismedit

Late onset neurological disorders, such as Parkinson's disease, may be partially due to glutamate binding NMDA and AMPA glutamate receptors37 In vitro spinal cord cultures with glutamate transport inhibitors led to degeneration of motor neurons, which was counteracted by some AMPA receptor antagonists such as GYKI 5246637 Research also suggests that the metabotropic glutamate receptor mGlu4 is directly involved in movement disorders associated with the basal ganglia through selectively modulating glutamate in the striatum64

Rasmussen's encephalitisedit

In 1994, GluR3 was shown to act as an autoantigen in Rasmussen's encephalitis, leading to speculation that autoimmune activity might underlie the condition33

Schizophreniaedit

In schizophrenia, the expression of the mRNA for the NR2A subunit of the NMDA glutamate receptor was found to be decreased in a subset of inhibitory interneurons in the cerebral cortex65 This is suggested by upregulation of GABA, an inhibitory neurotransmitter In schizophrenia, the expression of the NR2A subunit of NDMA receptors in mRNA was experimentally undetectable in 49-73% in GABA neurons that usually express it These are mainly in GABA cells expressing the calcium-buffering protein parvalbumin PV, which exhibits fast-spiking firing properties and target the perisomatic basket cells and axo-axonic chandelier cells compartments of pyramidal neurons65 The study found the density of NR2A mRNA-expressing PV neurons was decreased by as much as 50% in subjects with schizophrenia In addition, density of immunohistochemically labeled glutamatergic terminals with an antibody against the vesicular glutamate transporter vGluT1 also exhibited a reduction that paralleled the reduction in the NR2A-expressing PV neurons Together, these observations suggest glutamatergic innervation of PV-containing inhibitory neurons appears to be deficient in schizophrenia65 Expression of NR2A mRNA has also been found to be altered in the inhibitory neurons that contain another calcium buffer, calbindin, targeting the dendrites of pyramidal neurons,66 and the expression of the mRNA for the GluR5 kainate receptor in GABA neurons has also been found to be changed in organisms with schizophrenia67 Current research is targeting glutamate receptor antagonists as potential treatments for schizophrenia Memantine, a weak, nonselective NMDA receptor antagonist, was used as an add-on to clozapine therapy in a clinical trial Refractory schizophrenia patients showed associated improvements in both negative and positive symptoms, underscoring the potential uses of GluR antagonists as antipsychotics68 Furthermore, administration of noncompetitive NMDA receptor antagonists have been tested on rat models Scientists proposed that specific antagonists can act on GABAergic interneurons, enhancing cortical inhibition and preventing excessive glutamatergic transmission associated with schizophrenia These and other atypical antipsychotic drugs can be used together to inhibit excessive excitability in pyramidal cells, decreasing the symptoms of schizophrenia69

Seizuresedit

Glutamate receptors have been discovered to have a role in the onset of epilepsy NMDA and metabotropic types have been found to induce epileptic convulsions Using rodent models, labs have found that the introduction of antagonists to these glutamate receptors helps counteract the epileptic symptoms70 Since glutamate is a ligand for ligand-gated ion channels, the binding of this neurotransmitter will open gates and increase sodium and calcium conductance These ions play an integral part in the causes of seizures Group 1 metabotropic glutamate receptors mGlu1 and mGlu5 are the primary cause of seizing, so applying an antagonist to these receptors helps in preventing convulsions71

Other diseases suspected of glutamate receptor linkedit

Neurodegenerative diseases with a suspected excitotoxicity linkedit

Neurodegenerative diseases suspected to have a link mediated at least in part through stimulation of glutamate receptors:3572

  • AIDS dementia complex
  • Alzheimer's disease
  • Amyotrophic lateral sclerosis
  • Combined systems disease vitamin B12 deficiency
  • Depression/anxiety
  • Drug addiction, tolerance, and dependency
  • Glaucoma
  • Hepatic encephalopathy
  • Hydroxybutyric aminoaciduria
  • Hyperhomocysteinemia and homocysteinuria
  • Hyperprolinemia
  • Lead encephalopathy
  • Leber's disease
  • MELAS syndrome
  • MERRF
  • Mitochondrial abnormalities and other inherited or acquired biochemical disorders
  • Neuropathic pain syndromes eg causalgia or painful peripheral neuropathies
  • Nonketotic hyperglycinemia
  • Olivopontocerebellar atrophy some recessive forms
  • Essential tremor
  • Rett syndrome
  • Sulfite oxidase deficiency
  • Wernicke's encephalopathy

Otheredit

  • Depersonalization Disorder

See alsoedit

  • Antiglutamate receptor antibodies
  • Excitotoxicity
  • N-Methyl-D-aspartic acid
  • Glutamate transporter
  • Metabotropic glutamate receptor
  • Synaptic plasticity
  • Neurodegeneration
  • Glutamate receptor-interacting protein

Referencesedit

  1. ^ a b c Petroff OA December 2002 "GABA and glutamate in the human brain" Neuroscientist 8 6: 562–573 PMID 12467378 doi:101177/1073858402238515  Glutamate is the main excitatory and GABA the main inhibitory neurotransmitter in the mammalian cortex
  2. ^ "Glutamate Receptors - Structures and Functions" Centre of Synaptic Plasticity University of Bristol 2007-01-04 Retrieved 2009-12-07 
  3. ^ Watanabe M, Maemura K, Kanbara K, Tamayama T, Hayasaki H 2002 "GABA and GABA receptors in the central nervous system and other organs" Int Rev Cytol International Review of Cytology 213: 1–47 ISBN 978-0-12-364617-0 PMID 11837891 doi:101016/S0074-76960213011-7 
  4. ^ Debanne D, Daoudal G, Sourdet V, Russier M 2003 "Brain plasticity and ion channels" J Physiol Paris 97 4–6: 403–14 PMID 15242652 doi:101016/jjphysparis200401004 
  5. ^ Maren S, Tocco G, Standley S, Baudry M, Thompson RF 1993 "Postsynaptic factors in the expression of long-term potentiation LTP: increased glutamate receptor binding following LTP induction in vivo" Proceedings of the National Academy of Sciences 90 20: 9654–8 PMC 47628  PMID 8415757 doi:101073/pnas90209654 
  6. ^ Pérez-Otaño I, Ehlers MD May 2005 "Homeostatic plasticity and NMDA receptor trafficking" Trends Neurosci 28 5: 229–38 PMID 15866197 doi:101016/jtins200503004 
  7. ^ Asztély F, Gustafsson B February 1996 "Ionotropic glutamate receptors Their possible role in the expression of hippocampal synaptic plasticity" Mol Neurobiol 12 1: 1–11 PMID 8732537 doi:101007/BF02740744 
  8. ^ Weiler IJ, Greenough WT August 1993 "Metabotropic glutamate receptors trigger postsynaptic protein synthesis" Proc Natl Acad Sci USA 90 15: 7168–71 PMC 47097  PMID 8102206 doi:101073/pnas90157168 
  9. ^ a b Teichberg VI December 1991 "Glial glutamate receptors: likely actors in brain signaling" FASEB J 5 15: 3086–91 PMID 1660422 
  10. ^ a b c Steinhäuser C, Gallo V August 1996 "News on glutamate receptors in glial cells" Trends Neurosci 19 8: 339–45 PMID 8843603 doi:101016/0166-22369610043-6 
  11. ^ a b Palmada M, Centelles J 1998 "Excitatory amino acid neurotransmission Pathways for metabolism, storage and reuptake of glutamate in brain" Front Biosci 3: d701–18 PMID 9665875 
  12. ^ Ohashi H, Maruyama T, Higashi-Matsumoto H, Nomoto T, Nishimura S, Takeuchi Y 2002 "A novel binding assay for metabotropic glutamate receptors using 3H L-quisqualic acid and recombinant receptors" PDF Z Naturforsch C 57 3–4: 348–55 PMID 12064739 doi:101515/znc-2002-3-425 Subscription required help 
  13. ^ Suchanek B, Seeburg PH, Sprengel R January 1995 "Gene structure of the murine N-methyl D-aspartate receptor subunit NR2C" J Biol Chem 270 1: 41–4 PMID 7814402 doi:101074/jbc270141 
  14. ^ Goto H, Watanabe K, Araragi N, Kageyama R, Tanaka K, Kuroki Y, Toyoda A, Hattori M, Sakaki Y, Fujiyama A, Fukumaki Y, Shibata H 2009 "The identification and functional implications of human-specific "fixed" amino acid substitutions in the glutamate receptor family" BMC Evol Biol 9: 224 PMC 2753569  PMID 19737383 doi:101186/1471-2148-9-224 
  15. ^ Dingledine R, Borges K, Bowie D, Traynelis SF March 1999 "The glutamate receptor ion channels" Pharmacol Rev 51 1: 7–61 PMID 10049997 
  16. ^ Andersson O, Stenqvist A, Attersand A, von Euler G December 2001 "Nucleotide sequence, genomic organization, and chromosomal localization of genes encoding the human NMDA receptor subunits NR3A and NR3B" Genomics 78 3: 178–84 PMID 11735224 doi:101006/geno20016666 
  17. ^ Conn PJ, et al 2005 "Metabotropic glutamate receptors in the basal ganglia motor circuit" Nature Reviews Neuroscience 6 10: 787–98 PMID 16276355 doi:101038/nrn1763 
  18. ^ Johnson JW, Ascher P May 1990 "Voltage-dependent block by intracellular Mg2+ of N-methyl-D-aspartate-activated channels" Biophys J 57 5: 1085–90 Bibcode:1990BpJ571085J PMC 1280813  PMID 1692749 doi:101016/S0006-34959082626-6 
  19. ^ Crowder JM, Croucher MJ, Bradford HF, Collins JF June 1987 "Excitatory amino acid receptors and depolarization-induced Ca2+ influx into hippocampal slices" J Neurochem 48 6: 1917–24 PMID 2437250 doi:101111/j1471-41591987tb05756x 
  20. ^ Gover TD, Moreira TH, Weinreich D 2009 "Role of calcium in regulating primary sensory neuronal excitability" Handb Exp Pharmacol 194 194: 563–87 PMID 19655118 doi:101007/978-3-540-79090-7_16 
  21. ^ Barbado M, Fablet K, Ronjat M, De Waard M June 2009 "Gene regulation by voltage-dependent calcium channels" Biochim Biophys Acta 1793 6: 1096–104 PMID 19250948 doi:101016/jbbamcr200902004 
  22. ^ a b Muto T, Tsuchiya D, Morikawa K, Jingami H March 2007 "Structures of the extracellular regions of the group II/III metabotropic glutamate receptors" Proc Natl Acad Sci USA 104 10: 3759–64 PMC 1820657  PMID 17360426 doi:101073/pnas0611577104 
  23. ^ a b Pin JP, Acher F June 2002 "The metabotropic glutamate receptors: structure, activation mechanism and pharmacology" Curr Drug Targets CNS Neurol Disord 1 3: 297–317 PMID 12769621 doi:102174/1568007023339328 
  24. ^ Platt SR 2007 "The role of glutamate in central nervous system health and disease--a review" Vet J 173 2: 278–86 PMID 16376594 doi:101016/jtvjl200511007 
  25. ^ Kinnamon SC, Vandenbeuch A July 2009 "Receptors and transduction of umami taste stimuli" Ann N Y Acad Sci 1170: 55–9 PMID 19686108 doi:101111/j1749-6632200904106x 
  26. ^ Gill SS, Pulido OM, Mueller RW, McGuire PF July 1998 "Molecular and immunochemical characterization of the ionotropic glutamate receptors in the rat heart" Brain Res Bull 46 5: 429–34 PMID 9739005 doi:101016/S0361-92309800012-4 
  27. ^ a b Weaver CD, Yao TL, Powers AC, Verdoorn TA May 1996 "Differential expression of glutamate receptor subtypes in rat pancreatic islets" J Biol Chem 271 22: 12977–84 PMID 8662728 doi:101074/jbc2712212977 
  28. ^ Bertrand G, Gross R, Puech R, Loubatières-Mariani MM, Bockaert J June 1993 "Glutamate stimulates glucagon secretion via an excitatory amino acid receptor of the AMPA subtype in rat pancreas" Eur J Pharmacol 237 1: 45–50 PMID 7689469 doi:101016/0014-29999390091-U 
  29. ^ Weaver CD, Gundersen V, Verdoorn TA January 1998 "A high affinity glutamate/aspartate transport system in pancreatic islets of Langerhans modulates glucose-stimulated insulin secretion" J Biol Chem 273 3: 1647–53 PMID 9430708 doi:101074/jbc27331647 
  30. ^ Carlton SM, Hargett GL, Coggeshall RE September 1995 "Localization and activation of glutamate receptors in unmyelinated axons of rat glabrous skin" Neurosci Lett 197 1: 25–8 PMID 8545047 doi:101016/0304-39409511889-5 
  31. ^ Carlson NG, Gahring LC, Twyman RE, Rogers SW April 1997 "Identification of amino acids in the glutamate receptor, GluR3, important for antibody-binding and receptor-specific activation" J Biol Chem 272 17: 11295–301 PMID 9111034 doi:101074/jbc2721711295 
  32. ^ a b Gahring LC, Rogers SW, Twyman RE February 1997 "Autoantibodies to glutamate receptor subunit GluR2 in nonfamilial olivopontocerebellar degeneration" Neurology 48 2: 494–500 PMID 9040745 doi:101212/wnl482494 
  33. ^ a b Autoantibodies to glutamate receptor GluR3 in Rasmussen's encephalitis - 1994
  34. ^ He XP, Patel M, Whitney KD, Janumpalli S, Tenner A, McNamara JO January 1998 "Glutamate receptor GluR3 antibodies and death of cortical cells" Neuron 20 1: 153–63 PMID 9459451 doi:101016/S0896-62730080443-2 
  35. ^ a b Dubinsky JM February 1993 "Intracellular calcium levels during the period of delayed excitotoxicity" J Neurosci 13 2: 623–31 PMID 8093901 
  36. ^ Manev H, Favaron M, Guidotti A, Costa E July 1989 "Delayed increase of Ca2+ influx elicited by glutamate: role in neuronal death" Mol Pharmacol 36 1: 106–12 PMID 2568579 
  37. ^ a b c d e Meldrum B 1993 "Amino acids as dietary excitotoxins: a contribution to understanding neurodegenerative disorders" Brain Res Brain Res Rev 18 3: 293–314 PMID 8401596 doi:101016/0165-01739390014-Q 
  38. ^ Aoyama K, Watabe M, Nakaki T November 2008 "Regulation of neuronal glutathione synthesis" J Pharmacol Sci 108 3: 227–38 PMID 19008644 doi:101254/jphs08R01CR 
  39. ^ a b Markowitz AJ, White MG, Kolson DL, Jordan-Sciutto KL July 2007 "Cellular interplay between neurons and glia: toward a comprehensive mechanism for excitotoxic neuronal loss in neurodegeneration" Cellscience 4 1: 111–146 PMC 2613343  PMID 19122795 
  40. ^ Nicholls DG December 2009 "Spare respiratory capacity, oxidative stress and excitotoxicity" Biochem Soc Trans 37 Pt 6: 1385–8 PMID 19909281 doi:101042/BST0371385 
  41. ^ Hirsch JA, Gibson GE August 1984 "Selective alteration of neurotransmitter release by low oxygen in vitro" Neurochem Res 9 8: 1039–49 PMID 6149480 doi:101007/BF00964800 
  42. ^ Obrenovitch TP, Richards DA 1995 "Extracellular neurotransmitter changes in cerebral ischaemia" Cerebrovasc Brain Metab Rev 7 1: 1–54 PMID 7742171 
  43. ^ a b Beal MF December 1992 "Mechanisms of excitotoxicity in neurologic diseases" FASEB J 6 15: 3338–44 PMID 1464368 
  44. ^ Nechifor, Mihai "Magnesium in drug dependencies" Magnesium Research John Libbey Eurotext Retrieved 13 June 2013 
  45. ^ "Glutamate Receptor Summary Report" CureHunter Retrieved 2009-12-07 
  46. ^ Vadasz C, Saito M, Gyetvai BM, Oros M, Szakall I, Kovacs KM, Prasad VV, Toth R 2007 "Glutamate receptor metabotropic 7 is cis-regulated in the mouse brain and modulates alcohol drinking" Genomics 90 6: 690–702 doi:101016/jygeno200708006 
  47. ^ a b Elia J, Glessner JT, Wang K, Takahashi N, Shtir CJ, Hadley D, Sleiman PM, Zhang H, Kim CE, Robison R, et al January 2012 "Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder" Nat Genet 44 1: 78–84 PMID 22138692 doi:101038/ng1013 Lay summary – Genetic Engineering & Biotechnology News 
  48. ^ a b Schmeisser MJ, Ey E, Wegener S, Bockmann J, Stempel AV, Kuebler A, Janssen AL, Udvardi PT, Shiban E, Spilker C, et al June 2012 "Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2" Nature 486 7402: 256–60 PMID 22699619 doi:101038/nature11015 Lay summary – AlphaGalileo Foundation 
  49. ^ Plumb B "Glutamate - A Pain Transmitter Your Subconscious May Be Able To Limit" EzineArticlescom  Missing or empty |url= help; |access-date= requires |url= help
  50. ^ Dorval KM, Wigg KG, Crosbie J, Tannock R, Kennedy JL, Ickowicz A, Pathare T, Malone M, Schachar R, Barr CL July 2007 "Association of the glutamate receptor subunit gene GRIN2B with attention-deficit/hyperactivity disorder" Genes Brain Behav 6 5: 444–52 PMID 17010153 doi:101111/j1601-183X200600273x 
  51. ^ a b Gainetdinov RR, Mohn AR, Bohn LM, Caron MG September 2001 "Glutamatergic modulation of hyperactivity in mice lacking the dopamine transporter" Proc Natl Acad Sci USA 98 20: 11047–54 PMC 58681  PMID 11572967 doi:101073/pnas191353298 
  52. ^ Turic D, Langley K, Williams H, Norton N, Williams NM, Moskvina V, Van den Bree MB, Owen MJ, Thapar A, O'Donovan MC June 2005 "A family based study implicates solute carrier family 1-member 3 SLC1A3 gene in attention-deficit/hyperactivity disorder" Biol Psychiatry 57 11: 1461–6 PMID 15950021 doi:101016/jbiopsych200503025 
  53. ^ Osherovich L 2012 "Fine-tuning mGluRs" Science-Business eXchange 5 1 doi:101038/scibx20123 
  54. ^ Chez, MG; Burton, Q; Dowling, T; Chang, M; Khanna, P; Kramer, C May 2007 "Memantine as adjunctive therapy in children diagnosed with autistic spectrum disorders: an observation of initial clinical response and maintenance tolerability" Journal of child neurology 22 5: 574–9 PMID 17690064 doi:101177/0883073807302611 
  55. ^ Erickson, CA; Posey, DJ; Stigler, KA; Mullett, J; Katschke, AR; McDougle, CJ March 2007 "A retrospective study of memantine in children and adolescents with pervasive developmental disorders" Psychopharmacology 191 1: 141–7 PMID 17016714 doi:101007/s00213-006-0518-9 
  56. ^ "A Study of Memantine Hydrochloride Namenda® for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders" 
  57. ^ Trudeau F, Gagnon S, Massicotte G April 2004 "Hippocampal synaptic plasticity and glutamate receptor regulation: influences of diabetes mellitus" Eur J Pharmacol 490 1–3: 177–86 PMID 15094084 doi:101016/jejphar200402055 
  58. ^ Diguet E, Fernagut PO, Normand E, Centelles L, Mulle C, Tison F April 2004 "Experimental basis for the putative role of GluR6/kainate glutamate receptor subunit in Huntington's disease natural history" Neurobiol Dis 15 3: 667–75 PMID 15056475 doi:101016/jnbd200312010 
  59. ^ Wu J, Tang T, Bezprozvanny I October 2006 "Evaluation of clinically relevant glutamate pathway inhibitors in in vitro model of Huntington's disease" Neurosci Lett 407 3: 219–23 PMID 16959411 doi:101016/jneulet200608036 Lay summary – Innovations Report 
  60. ^ Nishizawa Y 2001 "Glutamate release and neuronal damage in ischemia" Life Sci 69 4: 369–81 PMID 11459428 doi:101016/S0024-32050101142-0 
  61. ^ a b Ottersen OP "Sources of Glutamate in Ischemia" Neurodegeneration Research Group University of Oslo Retrieved 2009-12-07 
  62. ^ Meldrum BS 2000 "Glutamate as a neurotransmitter in the brain: review of physiology and pathology" J Nutr 130 4S Suppl: 1007S–15S PMID 10736372 
  63. ^ a b Bolton C; Paul C 2006 "Glutamate receptors in neuroinflammatory demyelinating disease" Mediators of Inflammation 2006 2: 93684 PMC 1592583  PMID 16883070 doi:101155/MI/2006/93684 
  64. ^ Cuomo D, et al 2009 "Metabotropic glutamate receptor subtype 4 selectively modulates both glutamate and GABA transmission in the striatum: implications for Parkinson's disease treatment" J Neurochem 109 4: 1096–105 PMID 19519781 doi:101111/j1471-4159200906036x 
  65. ^ a b c Bitanihirwe BK, Lim MP, Kelley JF, Kaneko T, Woo TU November 2009 "Glutamatergic deficits and parvalbumin-containing inhibitory neurons in the prefrontal cortex in schizophrenia" BMC Psychiatry 9: 71 PMC 2784456  PMID 19917116 doi:101186/1471-244X-9-71 
  66. ^ Woo TU, Shrestha K, Lamb D, Minns MM, Benes FM April 2008 "N-Methyl-D-Aspartate Receptor and Calbindin-Containing Neurons in the Anterior Cingulate Cortex in Schizophrenia and Bipolar Disorder" Biol Psychiatry 64 9: 803–809 PMID 18585682 doi:101016/jbiopsych200804034 
  67. ^ Woo TU, Shrestha K, Armstrong C, Minns MM, Walsh JP, Benes FM August 2007 "Differential alterations of kainate receptor subunits in inhibitory interneurons in the anterior cingulate cortex in schizophrenia and bipolar disorder" Schizophrenia Research 96 1–3: 46–61 PMC 2712609  PMID 17698324 doi:101016/jschres200706023 
  68. ^ de Lucena D, Fernandes BS, Berk M, et al October 2009 "Improvement of negative and positive symptoms in treatment-refractory schizophrenia: a double-blind, randomized, placebo-controlled trial with memantine as add-on therapy to clozapine" J Clin Psychiatry 70 10: 1416–23 PMID 19906345 doi:104088/JCP08m04935gry 
  69. ^ López-Gil X, Artigas F, Adell A November 2009 "Unraveling Monoamine Receptors Involved in the Action of Typical and Atypical Antipsychotics on Glutamatergic and Serotonergic Transmission in Prefrontal Cortex" Curr Pharm Des 16 5: 502–15 PMID 19909228 doi:102174/138161210790361416 
  70. ^ Chapman AG April 2000 "Glutamate and epilepsy" J Nutr 130 4S Suppl: 1043S–5S PMID 10736378 
  71. ^ Moldrich RX, Chapman AG, De Sarro G, Meldrum BS August 2003 "Glutamate metabotropic receptors as targets for drug therapy in epilepsy" Eur J Pharmacol 476 1–2: 3–16 PMID 12969743 doi:101016/S0014-29990302149-6 
  72. ^ Gillessen T, Budd SL, Lipton SA 2002 "Excitatory amino acid neurotoxicity" Adv Exp Med Biol 513: 3–40 PMID 12575816 doi:101007/978-1-4615-0123-7_1 

External linksedit

  • Glutamate Receptors at the US National Library of Medicine Medical Subject Headings MeSH
  • "Metabotropic Glutamate Receptors" IUPHAR Database of Receptors and Ion Channels International Union of Basic and Clinical Pharmacology 

glutamate receptor and immune system, glutamate receptor antagonists, glutamate receptor blockers, glutamate receptor gene on hippocampus, glutamate receptor mechanism, glutamate receptor perfusion speeds, glutamate receptor structure, glutamate receptor subunits, glutamate receptor trafficking in neurons, glutamate receptors


Glutamate receptor Information about

Glutamate receptor


  • user icon

    Glutamate receptor beatiful post thanks!

    29.10.2014


Glutamate receptor
Glutamate receptor
Glutamate receptor viewing the topic.
Glutamate receptor what, Glutamate receptor who, Glutamate receptor explanation

There are excerpts from wikipedia on this article and video

Random Posts

Book

Book

A book is a set of written, printed, illustrated, or blank sheets, made of ink, paper, parchment, or...
Boston Renegades

Boston Renegades

Boston Renegades was an American women’s soccer team, founded in 2003 The team was a member of the U...
Sa Caleta Phoenician Settlement

Sa Caleta Phoenician Settlement

Sa Caleta Phoenician Settlement can be found on a rocky headland about 10 kilometers west of Ibiza T...
Bodybuilding.com

Bodybuilding.com

Bodybuildingcom is an American online retailer based in Boise, Idaho, specializing in dietary supple...