Affinage

GRIK1

Glutamate receptor ionotropic, kainate 1 · UniProt P39086

Length
918 aa
Mass
104.0 kDa
Annotated
2026-06-10
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRIK1/GluK1 (originally GluR5) encodes a kainate-type ionotropic glutamate receptor subunit that assembles into homomeric or heteromeric ligand-gated cation channels and shapes both excitatory and inhibitory transmission across hippocampus, amygdala, spinal cord, and sensory ganglia (PMID:1977421, PMID:9335499, PMID:9849665). It coassembles promiscuously with other kainate subunits—KA2, GluK2/GluR6, and GluK3/GluR7—generating heteromeric channels whose desensitization, rectification, and agonist responses differ from the homomers (PMID:9254673, PMID:10493729, PMID:10627597). A defining function is the depolarization of GABAergic interneurons: GluK1-containing receptors on interneurons in CA1 and the basolateral amygdala drive repetitive firing and elevate tonic GABAergic inhibition onto principal neurons, positioning the subunit as a regulator of inhibitory circuit tone and network excitability, with genetic ablation increasing susceptibility to epileptiform activity and anxiety-like behavior (PMID:10196544, PMID:15509753, PMID:17245443). Presynaptic GluK1 also depresses excitatory transmission (PMID:9849664). Beyond ionotropic gating, GluK1 signals metabotropically through Goα proteins identified at its C-terminal domain (PMID:25834043), and on spinal axons couples to a pertussis-toxin-sensitive G protein/PLC/IP3 pathway in association with nNOS to mobilize internal Ca2+ (PMID:19224531). Channel properties are tuned post-transcriptionally and by accessory proteins: ADAR-mediated RNA editing at the Q/R site, which requires a distant intronic editing-site complementary sequence, reduces Ca2+ permeability and current density (PMID:8700852, PMID:10516295), while the auxiliary subunits NETO1 and NETO2 promote surface expression and synaptic targeting and bidirectionally control desensitization kinetics via their extracellular CUB domains (PMID:21593317, PMID:26720915, PMID:26277340). Surface delivery is gated by an ER retention signal centered on Arg-896 in the alternatively spliced C-terminal domain (PMID:14527949) and repressed in trans by the receptor's own cleaved signal peptide binding the amino-terminal domain (PMID:30451858). Ligand selectivity and gating are structurally explained by Ser741 in the ligand-binding domain and a binding cavity 40% larger than the AMPA receptor GluR2, with distinct domain-closure and antagonist-binding modes (PMID:12488532, PMID:15721240, PMID:16540562). Functionally, GluK1 mediates inflammatory/chemical nociception and confers neuroprotection in ischemia by suppressing Src-mediated NMDA receptor phosphorylation through GABAergic signaling (PMID:15673679, PMID:18678878).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1990 High

    Establishing that GluR5 is itself a functional ligand-gated channel subunit answered whether this AMPA-related clone formed glutamate-responsive channels at all.

    Evidence Xenopus oocyte expression and electrophysiology of homomeric GluR5

    PMID:1977421

    Open questions at the time
    • Native subunit composition and in vivo channel partners not addressed
    • Weak homomeric responses left physiological role unresolved
  2. 1996 High

    Defining the editing substrate showed how Q/R-site recoding is achieved, identifying the distant intronic ECS and ADAR as the machinery controlling receptor permeability.

    Evidence Minigene transfection, RT-PCR, and ADAR coexpression in heterologous cells

    PMID:8700852

    Open questions at the time
    • In vivo editing extent across tissues not quantified here
    • Functional consequence of editing on channel biophysics established only later
  3. 1997 High

    Pharmacological and mutagenic dissection established GluK1 as a regulator of inhibitory transmission and mapped residues controlling agonist selectivity and desensitization, moving from a cloned subunit to a circuit element with defined molecular determinants.

    Evidence Hippocampal slice electrophysiology with selective tools (ATPA, LY294486); chimeric and point-mutant receptors with patch-clamp

    PMID:9254673 PMID:9335499 PMID:9354337

    Open questions at the time
    • Pre- vs postsynaptic localization not yet resolved in 1997
    • Native heteromer composition inferred but not exhaustively defined
  4. 1998 High

    Cellular recordings localized GluK1 actions to identified interneurons and presynaptic terminals, showing it both drives tonic GABAergic inhibition and presynaptically depresses excitatory transmission, and mediates calcium-permeable excitation in the amygdala.

    Evidence Hippocampal and amygdala slice electrophysiology with paired-pulse facilitation and selective antagonists

    PMID:10196544 PMID:9849664 PMID:9849665

    Open questions at the time
    • Subunit stoichiometry of native receptors not defined
    • Molecular basis of presynaptic vs postsynaptic targeting unknown
  5. 1999 High

    Heteromeric assembly rules and the functional impact of Q/R editing were established, explaining how subunit mixing and recoding diversify native receptor kinetics and current density.

    Evidence Heterologous coexpression with polyamine rectification assays; knock-in mice editing the Q/R site with DRG electrophysiology; double in situ hybridization

    PMID:10493729 PMID:10516295 PMID:10627597

    Open questions at the time
    • Stoichiometry of native heteromers in vivo not measured
    • Editing dynamics under physiological/pathological states not addressed
  6. 2003 High

    The C-terminal ER retention signal and ligand-binding determinants were mapped, explaining how surface delivery is gated and how GluK1 achieves subtype-selective pharmacology, alongside identification of a postsynaptic GluK1 component in the amygdala.

    Evidence Site-directed mutagenesis with surface biotinylation; two-electrode voltage-clamp; whole-cell mEPSC analysis with topiramate; knockout-validated amygdala recordings

    PMID:12488532 PMID:12904467 PMID:14527949 PMID:19417176

    Open questions at the time
    • Trafficking factors recognizing the Arg-896 signal not identified
    • Coupling between retention signal and synaptic targeting unresolved
  7. 2005 High

    Crystal structures of the ligand-binding core and subunit-specific knockout phenotypes provided the structural and physiological basis for GluK1's distinct pharmacology and its specific roles in nociception and network regulation.

    Evidence X-ray crystallography of GluR5-S1S2 with multiple ligands; GluK1/GluK2 knockout mice with behavioral pain, fear, and network oscillation assays

    PMID:15509753 PMID:15673679 PMID:15710405 PMID:15721240

    Open questions at the time
    • Structures of intact channel and heteromers not resolved
    • Link between LBD structure and full-channel gating only inferred
  8. 2006 High

    Antagonist-bound structures revealed a binding mode that hyperextends the ligand-binding core, mechanistically connecting GluK1-selective antagonism to channel-closing conformational changes.

    Evidence X-ray crystallography of GluR5 LBD dimers with antagonists UBP302/UBP310

    PMID:16540562

    Open questions at the time
    • Conformational changes inferred from isolated LBD, not full-length channel
    • Antagonist effects on heteromeric receptors not addressed
  9. 2009 Medium

    GluK1 was shown to signal noncanonically and to confer neuroprotection, extending its function beyond ionotropic gating to metabotropic Ca2+ mobilization and modulation of NMDA receptor signaling.

    Evidence Confocal Ca2+ imaging with pertussis toxin and IP3 blockers plus co-IP in spinal axons; in vivo ischemia model with co-IP and phospho-Western blotting

    PMID:18678878 PMID:19224531

    Open questions at the time
    • Single-lab mechanistic chains awaiting independent replication
    • Identity of the relevant G protein/effector in the metabotropic pathway not fully defined at this stage
  10. 2015 High

    Auxiliary NETO proteins and a Goα partner were established as principal regulators of GluK1 trafficking, synaptic targeting, kinetics, and metabotropic signaling, defining the accessory machinery governing receptor behavior.

    Evidence Null-background CA1 expression with chimeric Neto constructs and electrophysiology; proteomic C-terminal pull-down with co-IP, BRET, and knockout validation

    PMID:21593317 PMID:25834043 PMID:26277340 PMID:26720915

    Open questions at the time
    • Mechanism by which NETO directs GluK1 to silent synapses unresolved
    • Downstream effectors of Goα signaling not mapped
  11. 2018 High

    A trans-acting repression mechanism was uncovered in which the cleaved signal peptide binds the ATD to suppress surface and synaptic targeting, revealing a novel layer of GluK1 trafficking control.

    Evidence Chimeric receptor and signal-peptide co-expression in CA1 neurons with EPSC recordings

    PMID:30451858

    Open questions at the time
    • Structural basis of signal-peptide/ATD interaction not solved
    • Physiological regulation of this repression in vivo unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GluK1's ionotropic and metabotropic signaling modes, editing state, and NETO-dependent trafficking are coordinated within native synapses, and whether GRIK1 variants cause defined human disease, remains unresolved.
  • No structure of the intact full-length or NETO-bound channel in the corpus
  • Downstream Goα effector pathway uncharacterized
  • No Mendelian disease link established in the timeline

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 3 GO:0060089 molecular transducer activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 2 R-HSA-8953854 Metabolism of RNA 2
Partners
GNAO1GRIK2GRIK5NETO1NETO2NOS1
Complex memberships
GluK1/GluK2 heteromeric kainate receptorGluK1/KA2 kainate receptor

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 GluR5 (GRIK1) forms homomeric ion channels in Xenopus oocytes that are weakly responsive to L-glutamate, establishing it as a ligand-gated ion channel subunit with approximately 40-41% amino acid identity to AMPA receptor subunits GluR1-4. Xenopus oocyte expression, electrophysiology Neuron High 1977421
1996 RNA editing at the Q/R site of GluR5 pre-mRNA requires a distant intronic editing site complementary sequence (ECS) located up to 1900 nucleotides distal to the Q/R site; the exon-intron duplex is a substrate for double-stranded RNA-specific adenosine deaminase (ADAR), which preferentially targets the adenosine at the Q/R site when coexpressed in HEK293 cells. Minigene transfection in PC-12 cells, RT-PCR, ADAR coexpression in HEK293 cells Proceedings of the National Academy of Sciences of the United States of America High 8700852
1997 Amino acids in the region between M3 and M4 of GluR5/GluR6 control agonist selectivity and desensitization: a single amino acid (N721 in GluR6; corresponding GluR5 residue) controls AMPA sensitivity and domoate deactivation rates, while A689 in GluR6 controls kainate desensitization rate. Chimeric receptor construction, site-directed mutagenesis, patch-clamp electrophysiology in heterologous cells Neuron High 9354337
1997 GluR5-containing kainate receptors regulate synaptic inhibition in the CA1 hippocampus by activating interneurons, demonstrated using selective agonist ATPA and antagonist LY294486. Hippocampal slice electrophysiology with selective pharmacological tools (ATPA agonist, LY294486 antagonist) Nature High 9335499
1997 GluR5 and KA-2 subunits coassemble to form functional heteromeric kainate receptor channels in trigeminal ganglion neurons, with pharmacological properties, desensitization, rectification, and ion permeability matching recombinant GluR5(R)/KA-2 channels. RT-PCR subunit expression profiling, patch-clamp electrophysiology of native neurons vs. recombinant receptors The Journal of neuroscience Medium 9254673
1998 GluR5-containing kainate receptors on CA1 inhibitory interneurons generate inward currents and repetitive action potentials upon activation by glutamate, kainate, or ATPA, causing a massive increase in tonic GABAergic inhibition onto pyramidal neuron somata and apical dendrites. Hippocampal slice electrophysiology, selective pharmacology (ATPA, LY293558), identified interneuron recordings Nature neuroscience High 10196544
1998 GluR5 subunits comprise or contribute to a presynaptic kainate receptor that depresses excitatory synaptic transmission in both CA1 and CA3 hippocampal regions; depression was associated with increased paired-pulse facilitation, indicating a presynaptic locus. Hippocampal slice field recordings and whole-cell voltage-clamp with selective agonist ATPA and antagonist LY294486 Neuropharmacology High 9849664
1998 GluR5 subunit mediates synaptic excitation in the rat basolateral amygdala (BLA); train-evoked, AMPA-receptor-independent synaptic responses are blocked by selective GluR5 antagonist LY293558 (95% block at 10 µM), with a null potential near 0 mV consistent with inwardly rectifying, calcium-permeable channels. Intracellular recording in BLA slices, selective pharmacological isolation of receptor component Neuropharmacology High 9849665
1999 GluR5, GluR6, and GluR7 kainate receptor subunits coassemble promiscuously to form heteromeric receptors; GluR5/GluR6 heteromers exhibit reduced desensitization and faster recovery from desensitization compared to homomeric GluR5, and coexpression of GluR6 enhances response magnitude to GluR5-selective agonists. Coexpression in HEK293 cells, patch-clamp electrophysiology, polyamine rectification assay to detect heteromeric assembly The Journal of neuroscience High 10493729
1999 RNA editing at the Q/R site of GluR5 reduces kainate receptor current density approximately 6-fold in dorsal root ganglion neurons, established using knock-in mice encoding arginine (edited) at position 636 (GluR5 Q/R site). Knock-in mouse genetics, patch-clamp electrophysiology in acutely isolated DRG neurons The Journal of neuroscience High 10516295
2000 GluR5 and GluR6 subunits coexist in a population of hippocampal GABAergic interneurons and coassemble into functional heteromeric receptors in HEK293 cells; heteromeric GluR5/GluR6 receptors show outward rectification, sensitivity to ATPA and AMPA, and distinct desensitization/gating properties from homomeric GluR6. Non-radioactive double in situ hybridization, cotransfection in HEK293 cells, patch-clamp electrophysiology The Journal of neuroscience High 10627597
2003 GluR5-2b subunit cell surface expression is controlled by an endoplasmic reticulum (ER) retention signal in its alternatively spliced C-terminal domain; a critical arginine (Arg-896) mediates ER retention, and phosphomimetic mutation at Thr-898 promotes ER exit and surface expression; two additional positively charged residues (Arg-900, Lys-901) also regulate ER export. Site-directed mutagenesis, cell surface biotinylation, immunofluorescence in heterologous cells and neurons The Journal of biological chemistry High 14527949
2003 Topiramate selectively inhibits postsynaptic GluR5 kainate receptor-mediated synaptic currents in rat BLA principal neurons (IC50 ~0.5 µM) without affecting paired-pulse facilitation, demonstrating a postsynaptic mechanism; it reduces miniature EPSC amplitude without affecting frequency. Whole-cell voltage-clamp recordings in rat BLA slices, pharmacological isolation of receptor subtypes The Journal of neuroscience High 12904467
2003 Selective activation of GluR5 on BLA interneurons depolarizes them and increases GABA release, leading to tonic GABA current and reduced excitability; this GluR5-mediated pathway activates voltage-dependent calcium channels and requires Ca2+ influx. Whole-cell recordings in amygdala slices, selective pharmacology, GluR5-/- mice The Journal of pharmacology and experimental therapeutics Medium 19417176
2003 GluR5 agonist selectivity over AMPA receptors is controlled by Ser741 in GluR5 (vs. Met722 in GluR1): mutation of Ser741 abolishes ATPA selectivity, demonstrating that a serine-dependent stabilization of active receptor conformation and steric clash with Met722 underlie GluR5 selectivity. Site-directed mutagenesis, two-electrode voltage-clamp in Xenopus oocytes Molecular pharmacology High 12488532
2004 GluK1 (GluR5) kainate receptors play a distinct role from GluR6 in hippocampal network activity: ablation of GluR5 increases susceptibility to kainate-induced gamma oscillations and epileptiform bursts, while GluR6 deletion prevents these effects, suggesting GluR5-containing receptors on interneuron axons provide a regulatory brake on network excitability. Kainate receptor knockout mice, in vitro and in vivo electrophysiology, network oscillation analysis The Journal of neuroscience High 15509753
2005 Crystal structures of the GluR5 ligand-binding core reveal a binding cavity 40% larger than GluR2, extensive interdomain contacts between domains 1 and 2 absent in AMPA receptors, and high-stability kainate complexes; the degree of domain closure by partial agonists differs quantitatively from AMPA receptors, explaining subtype-selective agonist binding. X-ray crystallography of GluR5-S1S2 ligand-binding core in complex with glutamate, 2S,4R-4-methylglutamate, kainate, and quisqualate Neuron High 15721240
2005 Crystal structure of GluR5-S1S2 in complex with (S)-glutamate at 1.95 Å reveals two-domain architecture similar to GluR2, high degree of domain closure (26°), a novel dimer interface with different protomer arrangement compared to GluR2, and Ser741 forming an interdomain bridge stabilizing a water network. X-ray crystallography FEBS letters High 15710405
2005 GluR5 knockout mice show significantly reduced responses to capsaicin and inflammatory pain, but normal fear memory and normal amygdala synaptic potentiation, establishing a specific role for GluR5 in chemical/inflammatory nociception distinct from GluR6's role in fear memory. GluR5 and GluR6 knockout mice, behavioral pain assays (capsaicin, formalin), fear conditioning, amygdala LTP recordings The Journal of neuroscience High 15673679
2006 Crystal structures of GluR5 ligand-binding core with GluR5-selective antagonists UBP302 and UBP310 reveal a novel antagonist-binding mechanism that does not contact E723 (unlike all previous AMPA/kainate agonist/antagonist complexes), resulting in hyperextension of the ligand-binding core and a 22 Å extension of ion-channel linkers in dimer assemblies compared to the glutamate-bound form. X-ray crystallography of GluR5 LBD dimer complexes with antagonists The Journal of neuroscience High 16540562
2007 GluR5-containing kainate receptors selectively depolarize inhibitory interneurons in the basolateral amygdala, increasing GABA release and tonic inhibitory current onto principal neurons; genetic deletion of GluR5 or local antagonist injection increases anxiety-like behavior, placing GluR5 as a key regulator of inhibitory circuit tone in the BLA. GluR5 knockout mice, whole-cell recordings in amygdala slices, intra-BLA drug injection, anxiety behavioral assays PloS one High 17245443
2008 GluR5-containing kainate receptor activation suppresses Src kinase-mediated tyrosine phosphorylation of NMDA receptor subunits NR2A and NR2B, and disrupts the NR2A-PSD-95-Src signaling complex, providing neuroprotection against ischemia-reperfusion injury; this occurs through GluR5-mediated Ca2+-dependent GABA release activating GABAA receptors, which then inhibit Src activation. In vivo rat ischemia model, co-immunoprecipitation, Western blotting for phosphorylated NR2A/NR2B, patch-clamp recording, GluR5 antisense oligodeoxynucleotides The Journal of biological chemistry Medium 18678878
2009 GluR5 kainate receptors on myelinated spinal cord axons mediate Ca2+ increase through both ionotropic and metabotropic (noncanonical) signaling via a pertussis toxin-sensitive G protein/PLC pathway causing IP3-dependent Ca2+ release from internal stores; GluR5 co-immunoprecipitates with nNOS and colocalizes with nNOS clusters on internodal axons, and the response involves intraaxonal NO. Confocal Ca2+ imaging in dorsal column axons, pertussis toxin treatment, IP3 receptor blockers, co-immunoprecipitation, immunohistochemistry Annals of neurology Medium 19224531
2011 NETO2 profoundly slows GluR1 (GluK1) kainate receptor desensitization, promotes plasma membrane localization, and targets GluK1-containing receptors to synapses in hippocampal neurons; NETO1 increases the rate of GluK1 desensitization. These auxiliary proteins extend the temporal range of receptor gating by over an order of magnitude. Heterologous cell transfection, hippocampal neuron transfection, whole-cell electrophysiology, immunocytochemistry for synaptic targeting The Journal of neuroscience High 21593317
2015 Both NETO1 and NETO2 profoundly increase GluK1 surface expression and drive GluK1 to synapses in hippocampal CA1 neurons; GluK1 synaptic targeting by Neto proteins is independent of their role in promoting surface trafficking. GluK1 is excluded from synapses expressing AMPA receptors and selectively incorporated into silent synapses. Neto2 slows GluK1 deactivation and desensitization; Neto1 speeds desensitization. CA1 pyramidal neuron expression (null background), whole-cell electrophysiology, surface expression assays, chimeric Neto constructs eLife High 26720915
2015 A proteomic screen of the GluK1 C-terminal domain identified Goα as an interacting partner; GluK1 activates Go proteins as validated by BRET experiments, and the interaction was confirmed by co-IP in native brain tissue and absent in GluK1-deficient mice, establishing GluK1 as capable of metabotropic (G protein) signaling via Go. Proteomics (C-terminal domain pull-down), co-immunoprecipitation in native brain, BRET assay, GluK1 knockout mice The Journal of neuroscience High 25834043
2015 NETO1 and NETO2 have distinct, subunit-dependent effects on GluK1 kinetics: both slow onset of desensitization at low agonist concentrations and increase glutamate sensitivity; at higher concentrations, Neto2 primarily slows desensitization while Neto1 primarily increases recovery from desensitization. The extracellular N-terminal CUB domain region of Neto is largely responsible for these distinct regulatory effects. Patch-clamp electrophysiology in HEK-293T cells expressing chimeric Neto1/Neto2 subunits with GluK1 or GluK2 Neuropharmacology Medium 26277340
2018 The cleaved signal peptide of GluK1 represses receptor surface trafficking and synaptic targeting by directly binding to the amino-terminal domain (ATD) in trans; replacing GluK1's signal peptide with GluK2's signal peptide increases synaptic EPSCs, and co-expression of GluK1 signal peptide suppresses this gain, establishing a novel trafficking repression mechanism. Chimeric receptor expression in hippocampal CA1 neurons, electrophysiology (EPSC recordings), co-expression assays Nature communications High 30451858

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 Cloning of a novel glutamate receptor subunit, GluR5: expression in the nervous system during development. Neuron 561 1977421
1997 A hippocampal GluR5 kainate receptor regulating inhibitory synaptic transmission. Nature 344 9335499
1998 GluR5 kainate receptor activation in interneurons increases tonic inhibition of pyramidal cells. Nature neuroscience 256 10196544
2005 Crystal structures of the GluR5 and GluR6 ligand binding cores: molecular mechanisms underlying kainate receptor selectivity. Neuron 225 15721240
2004 Distinct roles for the kainate receptor subunits GluR5 and GluR6 in kainate-induced hippocampal gamma oscillations. The Journal of neuroscience : the official journal of the Society for Neuroscience 176 15509753
2003 Selective antagonism of GluR5 kainate-receptor-mediated synaptic currents by topiramate in rat basolateral amygdala neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 162 12904467
2000 GluR5 and GluR6 kainate receptor subunits coexist in hippocampal neurons and coassemble to form functional receptors. The Journal of neuroscience : the official journal of the Society for Neuroscience 158 10627597
2014 Topiramate treatment for heavy drinkers: moderation by a GRIK1 polymorphism. The American journal of psychiatry 156 24525690
1993 Selective distribution of kainate receptor subunit immunoreactivity in monkey neocortex revealed by a monoclonal antibody that recognizes glutamate receptor subunits GluR5/6/7. The Journal of neuroscience : the official journal of the Society for Neuroscience 148 8392536
1998 Kainate GluR5 receptor subtype mediates the nociceptive response to formalin in the rat. Neuropharmacology 146 9680256
1996 Q/R site editing in kainate receptor GluR5 and GluR6 pre-mRNAs requires distant intronic sequences. Proceedings of the National Academy of Sciences of the United States of America 135 8700852
2004 LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well-tolerated in acute migraine. Cephalalgia : an international journal of headache 128 15196302
1998 The GluR5 subtype of kainate receptor regulates excitatory synaptic transmission in areas CA1 and CA3 of the rat hippocampus. Neuropharmacology 122 9849664
1999 Heteromeric kainate receptors formed by the coassembly of GluR5, GluR6, and GluR7. The Journal of neuroscience : the official journal of the Society for Neuroscience 113 10493729
1995 Distribution of the excitatory amino acid receptor subunits GluR2(4) in monkey hippocampus and colocalization with subunits GluR5-7 and NMDAR1. The Journal of neuroscience : the official journal of the Society for Neuroscience 113 7722624
1999 Q/R editing of the rat GluR5 and GluR6 kainate receptors in vivo and in vitro: evidence for independent developmental, pathological and cellular regulation. The European journal of neuroscience 109 10051761
1997 Identification of amino acid residues that control functional behavior in GluR5 and GluR6 kainate receptors. Neuron 109 9354337
1997 Glutamate receptor subunits GluR5 and KA-2 are coexpressed in rat trigeminal ganglion neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 106 9254673
2004 Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist. Neuropharmacology 104 15111016
2006 Crystal structures of the kainate receptor GluR5 ligand binding core dimer with novel GluR5-selective antagonists. The Journal of neuroscience : the official journal of the Society for Neuroscience 99 16540562
1996 Pharmacological discrimination of GluR5 and GluR6 kainate receptor subtypes by (3S,4aR,6R,8aR)-6-[2-(1(2)H-tetrazole-5-yl)ethyl]decahyd roisdoquinoline-3 carboxylic-acid. Molecular pharmacology 97 8609884
2005 Altered behavioral responses to noxious stimuli and fear in glutamate receptor 5 (GluR5)- or GluR6-deficient mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 94 15673679
1994 Assessing the extent of RNA editing in the TMII regions of GluR5 and GluR6 kainate receptors during rat brain development. Journal of neurochemistry 89 7512622
2011 Synaptic targeting and functional modulation of GluK1 kainate receptors by the auxiliary neuropilin and tolloid-like (NETO) proteins. The Journal of neuroscience : the official journal of the Society for Neuroscience 86 21593317
2009 Glutamate receptors on myelinated spinal cord axons: II. AMPA and GluR5 receptors. Annals of neurology 84 19224531
1998 GluR5 kainate receptor mediated synaptic transmission in rat basolateral amygdala in vitro. Neuropharmacology 83 9849665
2005 Crystal structure of the kainate receptor GluR5 ligand-binding core in complex with (S)-glutamate. FEBS letters 77 15710405
1997 Allelic association of juvenile absence epilepsy with a GluR5 kainate receptor gene (GRIK1) polymorphism. American journal of medical genetics 77 9259378
2001 RNA editing at the Q/R site for the glutamate receptor subunits GLUR2, GLUR5, and GLUR6 in hippocampus and temporal cortex from epileptic patients. Neurobiology of disease 75 11442354
2007 Increased anxiety-like behavior and enhanced synaptic efficacy in the amygdala of GluR5 knockout mice. PloS one 67 17245443
2001 GluR5,6,7 subunit immunoreactivity on apical pyramidal cell dendrites in hippocampus of schizophrenics and manic depressives. Hippocampus 63 11732702
1993 The gene encoding the glutamate receptor subunit GluR5 is located on human chromosome 21q21.1-22.1 in the vicinity of the gene for familial amyotrophic lateral sclerosis. Proceedings of the National Academy of Sciences of the United States of America 62 8419920
2010 The GluK1 (GluR5) Kainate/{alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist LY293558 reduces soman-induced seizures and neuropathology. The Journal of pharmacology and experimental therapeutics 60 20962029
2009 Association of markers in the 3' region of the GluR5 kainate receptor subunit gene to alcohol dependence. Alcoholism, clinical and experimental research 57 19320626
1993 Expression and novel subunit isoforms of glutamate receptor genes GluR5 and GluR6. Neuroreport 56 8260617
2009 Topiramate reduces excitability in the basolateral amygdala by selectively inhibiting GluK1 (GluR5) kainate receptors on interneurons and positively modulating GABAA receptors on principal neurons. The Journal of pharmacology and experimental therapeutics 55 19417176
2002 Paradoxical anti-epileptic effects of a GluR5 agonist of kainate receptors. Journal of neurophysiology 55 12091575
2003 Cell surface expression of GluR5 kainate receptors is regulated by an endoplasmic reticulum retention signal. The Journal of biological chemistry 54 14527949
2003 GluR5 kainate receptors, seizures, and the amygdala. Annals of the New York Academy of Sciences 52 12724156
2001 Role of AMPA and GluR5 kainate receptors in the development and expression of amygdala kindling in the mouse. Neuropharmacology 51 11077068
1997 The synaptic activation of the GluR5 subtype of kainate receptor in area CA3 of the rat hippocampus. Neuropharmacology 51 9517417
1999 Generation and analysis of GluR5(Q636R) kainate receptor mutant mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 49 10516295
2004 Behavioural effects of the novel AMPA/GluR5 selective receptor antagonist NS1209 after systemic administration in animal models of experimental pain. Neuropharmacology 48 15275824
2003 Glutamate receptor RNA editing: a molecular analysis of GluR2, GluR5 and GluR6 in human brain tissues and in NT2 cells following in vitro neural differentiation. Brain research. Molecular brain research 46 14559151
1998 Heterogeneity of homomeric GluR5 kainate receptor desensitization expressed in HEK293 cells. The Journal of physiology 44 9824706
1993 Organization and quantitative analysis of kainate receptor subunit GluR5-7 immunoreactivity in monkey hippocampus. Brain research 44 8252413
2001 Immunocytochemical localization of kainate-selective glutamate receptor subunits GluR5, GluR6, and GluR7 in the cat retina. Brain research 43 11164787
2004 Modulation of excitatory synaptic transmission in the spinal substantia gelatinosa of mice deficient in the kainate receptor GluR5 and/or GluR6 subunit. The Journal of physiology 42 14724198
2002 Ethyl (3S,4aR,6S,8aR)-6-(4-ethoxycar- bonylimidazol-1-ylmethyl)decahydroiso-quinoline-3-carboxylic ester: a prodrug of a GluR5 kainate receptor antagonist active in two animal models of acute migraine. Journal of medicinal chemistry 42 12238915
1997 Developmental changes of RNA editing of glutamate receptor subunits GluR5 and GluR6: in vivo versus in vitro. Brain research. Developmental brain research 41 9051270
1996 RNA editing of glutamate receptor subunits GluR2, GluR5 and GluR6 in transient cerebral ischemia in the rat. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 41 8964793
1998 Kainate glutamate receptors (GluR5-7) in the rat arcuate nucleus: relationship to tanycytes, astrocytes, neurons and gonadal steroid receptors. Journal of neuroendocrinology 38 9630393
1997 Characterization of RNA editing of the glutamate-receptor subunits GluR5 and GluR6 in granule cells during cerebellar development. Brain research. Molecular brain research 38 9450685
1994 Extent of RNA editing of glutamate receptor subunit GluR5 in different brain regions of the rat. Cellular and molecular neurobiology 38 7536132
1998 LY339434, a GluR5 kainate receptor agonist. Neuropharmacology 37 9849663
1995 cDNA cloning and functional properties of human glutamate receptor EAA3 (GluR5) in homomeric and heteromeric configuration. Receptors & channels 36 8589992
2014 Role of GluK1 kainate receptors in seizures, epileptic discharges, and epileptogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience 35 24760837
2007 Genetic and pharmacological studies of GluR5 modulation of inhibitory synaptic transmission in the anterior cingulate cortex of adult mice. Developmental neurobiology 34 17443779
2014 GRIK1 genotype moderates topiramate's effects on daily drinking level, expectations of alcohol's positive effects and desire to drink. The international journal of neuropsychopharmacology 33 24786948
2005 Two prodrugs of potent and selective GluR5 kainate receptor antagonists actives in three animal models of pain. Journal of medicinal chemistry 32 15974569
2008 Neuroprotection of GluR5-containing kainate receptor activation against ischemic brain injury through decreasing tyrosine phosphorylation of N-methyl-D-aspartate receptors mediated by Src kinase. The Journal of biological chemistry 31 18678878
1999 [3H]ATPA: a high affinity ligand for GluR5 kainate receptors. Neuropharmacology 31 10608276
1994 Developmental changes in the extent of RNA editing of glutamate receptor subunit GluR5 in rat brain. Neuroscience letters 31 7970143
2015 Neto auxiliary proteins control both the trafficking and biophysical properties of the kainate receptor GluK1. eLife 30 26720915
2001 Association study of polymorphisms in the GluR5 kainate receptor gene (GRIK1) with schizophrenia. Psychiatric genetics 29 11702055
2006 Antiallodynic and antihyperalgesic effects of selective competitive GLUK5 (GluR5) ionotropic glutamate receptor antagonists in the capsaicin and carrageenan models in rats. The Journal of pharmacology and experimental therapeutics 28 16837561
2011 Antinociceptive effects of MSVIII-19, a functional antagonist of the GluK1 kainate receptor. Pain 27 21324591
2009 GluR5-mediated glutamate signaling regulates hypothalamo-pituitary-adrenocortical stress responses at the paraventricular nucleus and median eminence. Psychoneuroendocrinology 27 19450932
2004 The effect of a kainate GluR5 receptor antagonist on responses of spinothalamic tract neurons in a model of peripheral neuropathy in primates. Pain 27 15327819
1999 Resolution, absolute stereochemistry, and enantiopharmacology of the GluR1-4 and GluR5 antagonist 2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isoxazolyl]propionic acid. Chirality 27 10561704
2022 Barley GRIK1-SnRK1 kinases subvert a viral virulence protein to upregulate antiviral RNAi and inhibit infection. The EMBO journal 26 35929182
2008 Soman induces ictogenesis in the amygdala and interictal activity in the hippocampus that are blocked by a GluR5 kainate receptor antagonist in vitro. Neuroscience 26 19136046
2010 Binding site and ligand flexibility revealed by high resolution crystal structures of GluK1 competitive antagonists. Neuropharmacology 25 20558186
2000 4-Alkyl- and 4-cinnamylglutamic acid analogues are potent GluR5 kainate receptor agonists. Journal of medicinal chemistry 25 10821708
1996 Distribution of glutamate receptor subunit proteins GluR2(4), GluR5/6/7, and NMDAR1 in the canine and primate cerebral cortex: a comparative immunohistochemical analysis. Brain research 25 8813384
2004 Bioisosteric modifications of 2-arylureidobenzoic acids: selective noncompetitive antagonists for the homomeric kainate receptor subtype GluR5. Journal of medicinal chemistry 24 15615543
2000 Genomic organization, proposed alternative splicing mechanisms, and RNA editing structure of GRIK1. Cytogenetics and cell genetics 23 10828597
2002 Sequencing of the GRIK1 gene in patients with juvenile absence epilepsy does not reveal mutations affecting receptor structure. American journal of medical genetics 22 11920863
1995 Temporal analysis of the upregulation of GluR5 mRNA editing with age: regional evaluation. Brain research. Developmental brain research 22 7656430
2015 Modulation of nociceptive dural input to the trigeminocervical complex through GluK1 kainate receptors. Pain 21 25679470
2015 A rat model of nerve agent exposure applicable to the pediatric population: The anticonvulsant efficacies of atropine and GluK1 antagonists. Toxicology and applied pharmacology 21 25689173
2013 Cortical GluK1 kainate receptors modulate scratching in adult mice. Journal of neurochemistry 21 23786569
2012 Efficacy of the GluK1/AMPA receptor antagonist LY293558 against seizures and neuropathology in a soman-exposure model without pretreatment and its pharmacokinetics after intramuscular administration. The Journal of pharmacology and experimental therapeutics 21 23042954
2003 The selective activation of the glutamate receptor GluR5 by ATPA is controlled by serine 741. Molecular pharmacology 21 12488532
2015 A proteomic analysis reveals the interaction of GluK1 ionotropic kainate receptor subunits with Go proteins. The Journal of neuroscience : the official journal of the Society for Neuroscience 20 25834043
2015 The auxiliary subunits Neto1 and Neto2 have distinct, subunit-dependent effects at recombinant GluK1- and GluK2-containing kainate receptors. Neuropharmacology 20 26277340
2003 Kainate receptor (GluR5)-mediated disinhibition of responses in rat ventrobasal thalamus allows a novel sensory processing mechanism. The Journal of physiology 20 12909680
2000 4-Alkylidenyl glutamic acids, potent and selective GluR5 agonists. Bioorganic & medicinal chemistry letters 20 10969973
2018 Signal peptide represses GluK1 surface and synaptic trafficking through binding to amino-terminal domain. Nature communications 19 30451858
2014 Self-efficacy mediates the effects of topiramate and GRIK1 genotype on drinking. Addiction biology 19 25496338
2011 Selective kainate receptor (GluK1) ligands structurally based upon 1H-cyclopentapyrimidin-2,4(1H,3H)-dione: synthesis, molecular modeling, and pharmacological and biostructural characterization. Journal of medicinal chemistry 19 21619066
2003 (S)-2-Amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propionic acid, a potent and selective agonist at the GluR5 subtype of ionotropic glutamate receptors. Synthesis, modeling, and molecular pharmacology. Journal of medicinal chemistry 19 12672235
2009 The glutamate receptor GluR5 agonist (S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propionic acid and the 8-methyl analogue: synthesis, molecular pharmacology, and biostructural characterization. Journal of medicinal chemistry 18 19588945
2006 Presynaptic regulation of the inhibitory transmission by GluR5-containing kainate receptors in spinal substantia gelatinosa. Molecular pain 18 16948848
2011 Piperazine-2,3-dicarboxylic acid derivatives as dual antagonists of NMDA and GluK1-containing kainate receptors. Journal of medicinal chemistry 17 22111545
2001 Synthesis and receptor binding affinity of new selective GluR5 ligands. Bioorganic & medicinal chemistry 17 11354670
2011 Binding and selectivity of the marine toxin neodysiherbaine A and its synthetic analogues to GluK1 and GluK2 kainate receptors. Journal of molecular biology 16 21893069
2019 The kainate receptor antagonist UBP310 but not single deletion of GluK1, GluK2, or GluK3 subunits, inhibits MPTP-induced degeneration in the mouse midbrain. Experimental neurology 15 31513786
2003 2-arylureidobenzoic acids: selective noncompetitive antagonists for the homomeric kainate receptor subtype GluR5. Journal of medicinal chemistry 15 14667236
1994 Genetic and physical mapping of the GLUR5 glutamate receptor gene on human chromosome 21. Human genetics 15 7959697

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