Affinage

GRM8

Metabotropic glutamate receptor 8 · UniProt O00222

Length
908 aa
Mass
101.7 kDa
Annotated
2026-06-10
59 papers in source corpus 25 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRM8 encodes mGlu8, a presynaptically localized group III metabotropic glutamate receptor that acts as an inhibitory autoreceptor restraining excitatory neurotransmitter release at defined CNS synapses (PMID:8710211, PMID:12213276). Agonist binding requires closure of the receptor's Venus flytrap module: antagonists block activation by preventing lobe closure through ionic and steric hindrance, and mutating those contact residues converts antagonists into full agonists, establishing VFTM closure as the gating step for this family 3 GPCR (PMID:12151600); crystal structures of the human amino-terminal domain bound to L-AP4, L-glutamate, and the selective agonist DCPG rationalize group III and mGlu8-subtype selectivity (PMID:29402739, PMID:30365309). The receptor couples through pertussis-toxin-sensitive Gi/o proteins via Gβγ signaling, and in heterologous systems activates GIRK currents (PMID:9875342, PMID:15623786). At lateral perforant path–dentate gyrus terminals, mGlu8 produces near-complete inhibition of glutamate release without reducing presynaptic Ca2+ entry, instead lowering the apparent Ca2+ affinity of the release sensor and the maximal release rate in a manner resistant to adenylate cyclase inhibition—indicating a direct action on the release machinery (PMID:21903594). This presynaptic depression is selective and broadly distributed, demonstrated by knockout-confirmed, agonist-dependent suppression of transmission at lateral olfactory tract–piriform cortex, retino-collicular, retinal bipolar, amygdalar, and BNST synapses (PMID:12213276, PMID:12213277, PMID:18625254, PMID:21451497, PMID:20096339, PMID:23220400). Functionally, mGlu8 modulates stress and fear circuitry: agonist activation engages GABAergic neurons in stress-related regions, attenuates amygdalar sensory transmission to inhibit conditioned and contextual fear, and its loss heightens anxiety, while in the thalamic reticular nucleus parvalbumin-neuron mGlu8 restrains excitatory drive onto relay cells and supports sensorimotor gating (PMID:12213278, PMID:12213279, PMID:12907308, PMID:16188284, PMID:23664812, PMID:38918065). Beyond the CNS, mGlu8 negatively modulates TRPA1 in cutaneous nociceptors via the cAMP/PKA pathway (PMID:27497709), and in cancer cells it acts through cAMP and MAPK signaling with both tumor-suppressor and, via a gain-of-function variant, tumor-promoting effects (PMID:30391781, PMID:29885518).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1996 High

    Established where mGlu8 acts by showing it resides in presynaptic axon terminals of projection neurons, defining it as a candidate release-modulating autoreceptor.

    Evidence Immunohistochemistry and electron microscopy combined with lateral olfactory tract transection in rhinencephalon

    PMID:8710211

    Open questions at the time
    • Did not establish the downstream signaling or release-modulating function
    • No physiological readout of receptor activity
  2. 1998 High

    Defined the receptor's pharmacology and effector coupling, showing two C-terminal splice variants with identical agonist profiles and coupling to GIRK channels.

    Evidence RT-PCR, heterologous expression in HEK293 with chimeric Gαqi9, and Xenopus oocyte electrophysiology with Kir3.1/3.4

    PMID:9875342

    Open questions at the time
    • Functional significance of C-terminal splice variation unresolved
    • Native G-protein coupling not identified in this heterologous system
  3. 2002 High

    Defined the molecular gating mechanism by showing Venus flytrap closure is required for activation, with specific residues controlling antagonist-versus-agonist behavior.

    Evidence Site-directed mutagenesis, molecular modeling, and functional assay in heterologous expression

    PMID:12151600

    Open questions at the time
    • Did not resolve how VFTM closure propagates to the transmembrane domain
    • No structural confirmation at the time
  4. 2002 High

    Demonstrated native autoreceptor function with pathway selectivity, showing mGlu8 suppresses transmission specifically at lateral perforant path and retino-collicular synapses.

    Evidence Field EPSP recording in wild-type vs mGlu8 knockout slices with selective agonist DCPG and antagonist LY341495

    PMID:12213276 PMID:12213277

    Open questions at the time
    • Mechanism of release suppression not yet defined
    • Pathway selectivity basis unknown
  5. 2002 Medium

    Linked mGlu8 loss to anxiety behavior, connecting the receptor to emotional regulation in vivo.

    Evidence Behavioral phenotyping of independent mGlu8 knockout lines in the elevated plus maze

    PMID:12213278 PMID:12213279

    Open questions at the time
    • Single behavioral readout per study
    • Circuit responsible for the phenotype not identified
  6. 2003 Medium

    Connected receptor activation to stress circuitry and showed engagement of GABAergic neurons, and that mGlu8 function is downregulated in epilepsy.

    Evidence c-Fos immunohistochemistry in wild-type vs knockout mice with GABAergic markers; concentration-response fEPSP recordings in a pilocarpine epilepsy model

    PMID:12539201 PMID:12907308

    Open questions at the time
    • Causal contribution of GABAergic engagement to behavior not established
    • Mechanism of disease-associated downregulation unknown
  7. 2005 High

    Resolved the G-protein effector mechanism in primary cells and showed differential transmitter regulation through a cAMP/PKA arm.

    Evidence Microspectrofluorimetry of Ca2+ in rod photoreceptors with PTX, CTX, Gβγ-inhibiting peptide and suramin; in vivo PAG microdialysis with PKA inhibitor H-89; amygdala patch-clamp with paired-pulse analysis

    PMID:15623786 PMID:16084932 PMID:16188284

    Open questions at the time
    • Whether cAMP/PKA versus Ca2+-affinity mechanisms operate synapse-specifically not reconciled
    • Identity of native coupling Gi isoform inferred, not proven
  8. 2011 High

    Defined the core presynaptic mechanism: near-complete release inhibition by lowering Ca2+ sensitivity of the release sensor rather than reducing Ca2+ entry, independent of adenylate cyclase.

    Evidence Presynaptic Ca2+ imaging, mEPSC recording, quantitative Ca2+-dependence modeling and pharmacological dissection at hippocampal LPP synapses

    PMID:21451497 PMID:21903594

    Open questions at the time
    • Molecular target on the release machinery not identified
    • Reconciliation with cAMP/PKA-dependent effects elsewhere unresolved
  9. 2013 High

    Distinguished mGlu8 from mGlu7 in amygdala physiology and fear, assigning mGlu8 a selective role in contextual fear expression.

    Evidence Electrophysiology and intra-amygdala microinjection with fear behavior in mGlu7 and mGlu8 knockout mice

    PMID:23664812

    Open questions at the time
    • Synaptic basis of contextual-versus-cued specificity not defined
  10. 2016 Medium

    Extended mGlu8 function to peripheral nociception, showing negative modulation of TRPA1 via cAMP/PKA.

    Evidence DRG Ca2+ imaging, single-fiber recording, behavioral paw-withdrawal testing, and PKA inhibition

    PMID:27497709

    Open questions at the time
    • Single lab
    • Direct molecular link between PKA and TRPA1 not established
  11. 2018 Medium

    Provided structural basis for ligand selectivity and revealed non-neuronal cancer roles through cAMP and MAPK signaling.

    Evidence X-ray crystallography of human ATD bound to L-AP4, L-glutamate, and DCPG; CRISPR and RNAi/overexpression in lung cancer, neuroblastoma and glioma cells with pathway rescue

    PMID:29402739 PMID:29885518 PMID:30365309 PMID:30391781

    Open questions at the time
    • Opposing tumor-suppressor and tumor-promoter findings not mechanistically reconciled
    • Cancer signaling shown in single labs without in vivo confirmation
  12. 2024 High

    Assigned mGlu8 a cell-type-specific role in thalamic circuit gating and in disease-model plasticity, linking it to sensorimotor gating and ASD-relevant deficits.

    Evidence FISH, parvalbumin-specific and AAV-conditional knockout with patch-clamp, paired-pulse inhibition and open-field behavior in TRN; in vivo DG field recording and social behavior in the VPA rat model

    PMID:38849397 PMID:38918065

    Open questions at the time
    • Circuit mechanism translating TRN mGlu8 loss to gating deficits incomplete
    • Whether VPA-model effects generalize to other ASD models unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular target on the vesicle release machinery through which mGlu8 lowers Ca2+-sensor affinity, and how this adenylate-cyclase-independent action coexists with cAMP/PKA-dependent effects in other tissues, remain unidentified.
  • No defined effector at the release sensor
  • Synapse- and tissue-specific switching between effector arms unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-112316 Neuronal System 2 R-HSA-162582 Signal Transduction 2

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 mGluR8 is localized presynaptically in axon terminals of projection neurons of the main olfactory bulb (rhinencephalon), as demonstrated by loss of immunoreactivity in layer Ia of piriform cortex after lateral olfactory tract transection and electron microscopic visualization of immunoreactivity in axon terminals making asymmetric synapses. Immunohistochemistry, electron microscopy, and lesion/tract-transection experiment Neuroscience letters High 8710211
1998 mGluR8a and mGluR8b splice variants, which differ only in their C-terminal domains (last 16 amino acids replaced by 16 different amino acids via out-of-frame insertion), display identical pharmacological profiles when expressed heterologously, with rank order of potency DL-AP4 > L-SOP > glutamate and higher agonist potencies than mGluR7. In Xenopus oocytes co-expressed with Kir3.1/3.4, mGluR8 couples to GIRK currents, blocked by the group II/III antagonist CPPG. Reverse transcription-PCR, transient transfection in HEK293 cells with chimeric Gαqi9, Xenopus oocyte electrophysiology The European journal of neuroscience High 9875342
2002 The mGlu8 receptor Venus flytrap module (VFTM) closure is required for receptor activation. Antagonists ACPT-II and MAP4 prevent VFTM closure via ionic (Asp-309) and steric (Tyr-227) hindrance respectively; alanine substitution of these residues converts the antagonists into full agonists, demonstrating that VFTM closure is necessary for family 3 GPCR activation. Site-directed mutagenesis, molecular modeling, functional assay in heterologous expression system Proceedings of the National Academy of Sciences of the United States of America High 12151600
2002 mGlu8 receptors function as presynaptic autoreceptors selectively on lateral perforant path (LPP) afferents to the dentate gyrus. L-AP4 and the selective mGlu8 agonist DCPG suppress LPP-evoked fEPSPs in wild-type but not in mGlu8 knockout hippocampal slices; medial perforant path fEPSPs were unaffected by mGlu8 deletion. Field EPSP recording in hippocampal slices from wild-type and mGlu8 knockout mice, pharmacological dissection Neuropharmacology High 12213276
2002 mGlu8 receptor-deficient mice show increased anxiety-related behavior in the elevated plus maze (increased open arm avoidance and risk assessment), indicating mGlu8 plays a role in modulating responses to novel stressful environments. Behavioral phenotyping of mGlu8 knockout mice generated by homologous recombination Neuropharmacology Medium 12213278 12213279
2002 Selective activation of mGlu8 receptors by DCPG reduces excitatory synaptic transmission (fEPSPs evoked by optic tract stimulation) in the superficial superior colliculus, antagonized by LY341495 at concentrations selective for mGlu8, indicating mGlu8 modulates glutamate release in the retino-collicular pathway. Field EPSP recording in rat superior colliculus in vitro slice preparation with pharmacological antagonism Neuropharmacology Medium 12213277
2003 Systemic administration of the mGlu8 agonist (S)-3,4-DCPG induces c-Fos expression in stress-related brain regions (paraventricular hypothalamus, central amygdala, lateral parabrachial nucleus, locus coeruleus) in wild-type but not mGlu8 knockout mice; over 92% of c-Fos positive neurons in the central amygdala were GABAergic, indicating mGlu8 activation modulates inhibitory neuronal activity in stress circuits. c-Fos immunohistochemistry, pharmacological challenge in wild-type vs. mGlu8 knockout mice, GABAergic neuron co-localization Neuropharmacology High 12907308
2003 In a pilocarpine model of limbic epilepsy, mGluR8 function at lateral perforant path terminals is downregulated in rats with spontaneous recurrent seizures (SRS): maximal L-AP4- and PPG-mediated inhibition of fEPSPs is significantly reduced (50% to 26% for L-AP4), without change in EC50, indicating loss of mGluR8 receptor number/efficacy rather than affinity. Field EPSP recording in hippocampal slices, concentration-response curves, pharmacological antagonism Synapse Medium 12539201
2005 mGlu8 receptor activation via intra-PAG (periaqueductal gray) perfusion with (S)-3,4-DCPG increases extracellular glutamate and decreases GABA levels; these effects are blocked by the group III antagonist MSOP and by the PKA inhibitor H-89, implicating adenylate cyclase/PKA signaling downstream of mGlu8 in differential regulation of glutamate and GABA release at the PAG. In vivo microdialysis in rat PAG, pharmacological antagonism with MSOP, UBP1112, and PKA inhibitor H-89 Neuropharmacology Medium 16084932
2005 mGlu8 receptor activation by (S)-3,4-DCPG in the lateral amygdala attenuates synaptic transmission from sensory afferents presynaptically (increased paired-pulse facilitation, no postsynaptic effect), and inhibits acquisition and expression of conditioned fear (fear-potentiated startle) in vivo; LTP by tetanic stimulation was also inhibited. In vivo fear-potentiated startle, patch-clamp recording in amygdala slices, paired-pulse protocol Neuropharmacology Medium 16188284
2005 mGluR8 activation in rod photoreceptors (by L-AP4, L-SOP, or L-glutamate) decreases cytosolic Ca2+ influx via a pertussis toxin-sensitive Gi/o protein and via Gβγ subunit signaling; suramin (G protein uncoupler), pertussis toxin, and a Gβγ-inhibiting peptide all abolish this effect, while cholera toxin (Gs activator) has no effect, and the absence of Go and Gz proteins suggests Gi2 and/or transducin as the coupling G protein. Microspectrofluorimetry of cytosolic Ca2+ in isolated rod photoreceptors, pertussis toxin, cholera toxin, Gβγ-inhibiting peptide, suramin Investigative ophthalmology & visual science High 15623786
2008 Both mGluR4 and mGluR8 contribute to presynaptic inhibition of synaptic transmission at the lateral olfactory tract–piriform cortex synapse; the selective mGluR8 agonist DCPG (300 nM) suppresses transmission, and the mGluR4 positive allosteric modulator PHCCC potentiates L-AP4 inhibition at this synapse. Whole-cell patch-clamp recordings in piriform cortex pyramidal cells, selective agonists and allosteric modulators Neuropharmacology Medium 18625254
2011 mGluR8 mediates presynaptic depression of excitatory transmission in the bed nucleus of the stria terminalis (BNST): DCPG effects are absent in mGluR8 KO slices, associated with increased paired-pulse facilitation and decreased spontaneous EPSC frequency; this mGluR8-mediated suppression is disrupted by α1 adrenergic receptor activation and by both acute and chronic restraint stress in vivo, as well as in α2A AR KO mice. Electrophysiology in BNST slices from wild-type and mGlu8 KO mice, mGluR8 immunohistochemistry, pharmacological dissection with α1/α2 AR modulators, in vivo stress paradigms Neuropsychopharmacology High 21451497
2011 mGluR8 achieves nearly complete inhibition of glutamate release at hippocampal lateral perforant path synapses without affecting presynaptic Ca2+ entry, diffusion, or buffering; instead, it acts by decreasing the apparent Ca2+ affinity of the release sensor and reducing maximal release rate. This action is resistant to inhibitors of adenylate cyclase and may represent a direct effect on the release machinery. Presynaptic Ca2+ imaging, miniature EPSC recording, quantitative Ca2+ dependence modeling, pharmacological blockade of adenylate cyclase and G-protein pathways Cerebral cortex High 21903594
2013 mGlu8 but not mGlu7 ablation reduces contextual fear; mGlu8 agonist DCPG decreases synaptic transmission but not LTP at thalamo-lateral amygdala synapses, and intra-amygdala DCPG selectively reduces expression of contextual fear but not cued fear acquisition or expression, establishing distinct roles for mGlu7 and mGlu8 in amygdala synaptic physiology and fear behavior. Electrophysiology (LTP and synaptic transmission) in amygdala slices from mGlu7 and mGlu8 KO mice, intra-amygdala microinjection with behavioral fear testing Neuropharmacology High 23664812
2016 mGluR8 negatively modulates TRPA1 activity on cutaneous nociceptors: DCPG (mGluR8 agonist) reduces TRPA1-mediated Ca2+ mobilization (co-localization of TRPA1 and mGluR8 confirmed), reverses mustard-oil-induced mechanical hypersensitivity in vivo, and reduces nociceptor firing at the single-fiber level; PKA inhibitor RpCAMPS mimics the DCPG effect, implicating the cAMP/PKA pathway. Ca2+ imaging in dorsal root ganglion neurons, in vivo paw withdrawal threshold testing, single-fiber electrophysiology, PKA inhibition Neuroscience Medium 27497709
2018 The crystal structure of the human mGlu8 amino terminal domain (ATD) bound to L-AP4 and to L-glutamate was solved, revealing that L-glutamate binds differently in mGlu8 compared to mGlu1, and that both the electronic and steric properties of the distal phosphate of L-AP4 account for its group III selectivity. X-ray crystallography of recombinant human mGlu8 ATD Bioorganic & medicinal chemistry letters High 29402739
2018 Crystal structure of recombinant human mGlu8 ATD bound to (S)-DCPG was solved; the structure shows the largest lobe opening angle among known agonist-bound mGlu ATD structures, and the DCPG binding conformation differs substantially from homology-model predictions, rationalizing (S)-DCPG's high mGlu8 subtype selectivity. X-ray crystallography, homology modeling of other mGlu subtypes Journal of medicinal chemistry High 30365309
2018 GRM8 transcriptional activation in squamous cell lung cancer promotes tumor cell survival by inhibiting the cAMP pathway and activating the MAPK pathway; the SNV A112G identified in GRM8 activates downstream signaling and induces cell proliferation, reversed by cAMP stimulator and MEK inhibitor. CRISPR-Cas9 genome editing in patient-derived xenograft cells, cAMP and MAPK pathway assays, pharmacological rescue Cancer letters Medium 30391781
2018 mGluR8 downregulation in human neuroblastoma (SH-SY5Y) cells increases proliferation and chemoresistance (to staurosporine, doxorubicin, irinotecan, cisplatin) with decreased caspase, calpain, GSK-3β, Akt, and JNK activity; conversely, mGluR8 overexpression in glioma cells (U87-MG, LN18) decreases proliferation and increases apoptosis and chemosensitivity, identifying a tumor suppressor role. RNAi knockdown and cDNA overexpression, cell proliferation assays, caspase/calpain activity assays, kinase activity measurement Cancer letters Medium 29885518
2010 Selective activation of mGluR8 by DCPG reversibly reduces Off-light responses of retinal ganglion cells in wild-type but not mGluR8-deficient retinas by suppressing both excitatory and inhibitory synaptic conductances, indicating mGluR8 reduces glutamate release from bipolar cell terminals and possibly inhibitory transmitter release from amacrine cells. Extracellular and whole-cell light-evoked recording in wild-type and mGluR8 KO mouse retina Neuroscience High 20096339
2024 mGlu8 receptor activation (DCPG) in the dentate gyrus inhibits LTP in normal rats but enhances impaired LTP in VPA-exposed (autism model) rats at the perforant path–dentate gyrus synapse; intra-DG DCPG also reverses reduced social novelty preference in VPA-exposed rats, suggesting mGlu8 dysfunction contributes to impaired synaptic plasticity in this ASD model. In vivo hippocampal field recording with high-frequency stimulation, intra-DG microinjection, social behavior testing in VPA rat model Scientific reports Medium 38849397
2024 In the thalamic reticular nucleus (TRN), mGlu8 (grm8) mRNA is expressed in parvalbumin-positive cells of both TRN core and shell matrices and in cortical layers involved in corticothalamic signaling. Constitutive parvalbumin-specific mGlu8 knockout increases spontaneous excitatory drive onto dorsal thalamus relay cells and impairs sensorimotor gating (paired-pulse inhibition); TRN-conditional AAV-mediated grm8 knockdown produces hyperlocomotion and anxiolytic effects in repeated open field testing. Fluorescent in situ hybridization, conditional (AAV-CRE) and cell-type-specific constitutive knockout, whole-cell patch-clamp, paired-pulse inhibition, open field behavioral testing The Journal of neuroscience High 38918065
2012 DCPG at submicromolar concentrations selectively inhibits excitatory transmission in the lateral perforant path (LPP) via mGlu8; at concentrations >1 μM, DCPG produces additional non-selective effects in both LPP and medial perforant path (MPP) that are absent in mGlu8 KO but mediated primarily by mGlu2, as shown in mGlu2, mGlu4, and mGlu7 KO mice and an mGlu2-deficient rat substrain. Field EPSP recording in hippocampal slices from multiple receptor-specific knockout mice and a naturally mGlu2-deficient rat substrain Neuropharmacology High 23220400

Source papers

Stage 0 corpus · 59 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Suppression of alcohol self-administration and cue-induced reinstatement of alcohol seeking by the mGlu2/3 receptor agonist LY379268 and the mGlu8 receptor agonist (S)-3,4-DCPG. European journal of pharmacology 116 16324694
1998 Cloning and characterization of alternative mRNA forms for the rat metabotropic glutamate receptors mGluR7 and mGluR8. The European journal of neuroscience 108 9875342
2002 Closure of the Venus flytrap module of mGlu8 receptor and the activation process: Insights from mutations converting antagonists into agonists. Proceedings of the National Academy of Sciences of the United States of America 85 12151600
2002 Increased anxiety-related behavior in mice deficient for metabotropic glutamate 8 (mGlu8) receptor. Neuropharmacology 82 12213279
2005 Increased measures of anxiety and weight gain in mice lacking the group III metabotropic glutamate receptor mGluR8. The European journal of neuroscience 77 16045496
2002 Performance deficits of mGluR8 knockout mice in learning tasks: the effects of null mutation and the background genotype. Neuropharmacology 58 12213278
2009 Association of single nucleotide polymorphisms in a glutamate receptor gene (GRM8) with theta power of event-related oscillations and alcohol dependence. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 57 18618593
2005 Expression patterns of Group III metabotropic glutamate receptors mGluR4 and mGluR8 in multiple sclerosis lesions. Journal of neuroimmunology 56 15589052
2006 Effects of (S)-3,4-DCPG, an mGlu8 receptor agonist, on inflammatory and neuropathic pain in mice. Neuropharmacology 53 17113112
1996 Presynaptic localization of a metabotropic glutamate receptor, mGluR8, in the rhinencephalic areas: a light and electron microscope study in the rat. Neuroscience letters 51 8710211
2007 Evaluation of the mGlu8 receptor as a putative therapeutic target in schizophrenia. Brain research 49 17434465
2008 The association analysis of RELN and GRM8 genes with autistic spectrum disorder in Chinese Han population. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 48 17955477
2009 The effect of mGlu8 deficiency in animal models of psychiatric diseases. Genes, brain, and behavior 42 19740090
2004 Positive associations of polymorphisms in the metabotropic glutamate receptor type 8 gene (GRM8) with schizophrenia. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 42 15211621
2002 Modulation of lateral perforant path excitatory responses by metabotropic glutamate 8 (mGlu8) receptors. Neuropharmacology 42 12213276
2018 Genomic sequencing and editing revealed the GRM8 signaling pathway as potential therapeutic targets of squamous cell lung cancer. Cancer letters 36 30391781
2015 Significant association of GRM7 and GRM8 genes with schizophrenia and major depressive disorder in the Han Chinese population. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 35 26655190
1996 Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q. Genomics 35 8824806
2005 Differential roles of mGlu8 receptors in the regulation of glutamate and gamma-aminobutyric acid release at periaqueductal grey level. Neuropharmacology 34 16084932
2005 Effects of the mGluR8 agonist (S)-3,4-DCPG in the lateral amygdala on acquisition/expression of fear-potentiated startle, synaptic transmission, and plasticity. Neuropharmacology 33 16188284
2013 Differential roles of mGlu(7) and mGlu(8) in amygdala-dependent behavior and physiology. Neuropharmacology 32 23664812
2003 Systemic administration of the potent mGlu8 receptor agonist (S)-3,4-DCPG induces c-Fos in stress-related brain regions in wild-type, but not mGlu8 receptor knockout mice. Neuropharmacology 32 12907308
1997 The human metabotropic glutamate receptor 8 (GRM8) gene: a disproportionately large gene located at 7q31.3-q32.1. Genomics 32 9299241
2018 Effects of Sub-Chronic MPTP Exposure on Behavioral and Cognitive Performance and the Microbiome of Wild-Type and mGlu8 Knockout Female and Male Mice. Frontiers in behavioral neuroscience 27 30072879
2003 Down-regulation of mGluR8 in pilocarpine epileptic rats. Synapse (New York, N.Y.) 26 12539201
2017 Decreased anxiety, voluntary ethanol intake and ethanol-induced CPP acquisition following activation of the metabotropic glutamate receptor 8 "mGluR8". Pharmacology, biochemistry, and behavior 25 28322866
2004 Potential antipsychotic and extrapyramidal effects of (R,S)-3,4-dicarboxyphenylglycine [(R,S)-3,4-DCPG], a mixed AMPA antagonist/mGluR8 agonist. Polish journal of pharmacology 24 15215559
2011 mGluR8 modulates excitatory transmission in the bed nucleus of the stria terminalis in a stress-dependent manner. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 23 21451497
2005 Lack of the antianxiety-like effect of (S)-3,4-DCPG, an mGlu8 receptor agonist, after central administration in rats. Pharmacological reports : PR 22 16382208
2002 Reduction of excitatory transmission in the retino-collicular pathway via selective activation of mGlu8 receptors by DCPG. Neuropharmacology 22 12213277
2018 An endogenous and ectopic expression of metabotropic glutamate receptor 8 (mGluR8) inhibits proliferation and increases chemosensitivity of human neuroblastoma and glioma cells. Cancer letters 20 29885518
2017 A 7q31.33q32.1 microdeletion including LRRC4 and GRM8 is associated with severe intellectual disability and characteristics of autism. Human genome variation 19 28224041
2008 Metabotropic glutamate receptors mGluR4 and mGluR8 regulate transmission in the lateral olfactory tract-piriform cortex synapse. Neuropharmacology 19 18625254
2005 Interaction between mGluR8 and calcium channels in photoreceptors is sensitive to pertussis toxin and occurs via G protein betagamma subunit signaling. Investigative ophthalmology & visual science 18 15623786
2012 Characterisation of an mGlu8 receptor-selective agonist and antagonist in the lateral and medial perforant path inputs to the dentate gyrus. Neuropharmacology 16 23220400
2000 No association found between polymorphisms in genes encoding mGluR7 and mGluR8 and idiopathic generalised epilepsy in a case control study. Epilepsy research 16 10690750
2013 The role of rs2237781 within GRM8 in eating behavior. Brain and behavior 15 24392270
2002 No association between metabotropic glutamate receptors 7 and 8 (mGlur7 and mGlur8) gene polymorphisms and withdrawal seizures and delirium tremens in alcohol-dependent individuals. Alcohol and alcoholism (Oxford, Oxfordshire) 15 11912074
2013 Related functions of mGlu4 and mGlu8. Pharmacology, biochemistry, and behavior 14 23948069
2015 Further Analyses of Genetic Association Between GRM8 and Alcohol Dependence Symptoms Among Young Adults. Journal of studies on alcohol and drugs 11 25978827
2007 Anticonvulsive effect of a selective mGluR8 agonist (S)-3,4-dicarboxyphenylglycine (S-3,4-DCPG) in the mouse pilocarpine model of status epilepticus. Epilepsia 11 17430409
2024 Effects of (S)-3,4-DCPG, an mGlu8 receptor agonist, on hippocampal long-term potentiation at perforant pathway-dentate gyrus synapses in prenatal valproic acid-induced rat model of autism. Scientific reports 10 38849397
2018 Determination of L-AP4-bound human mGlu8 receptor amino terminal domain structure and the molecular basis for L-AP4's group III mGlu receptor functional potency and selectivity. Bioorganic & medicinal chemistry letters 10 29402739
2014 Association analysis of the GRM8 gene with schizophrenia in the Uygur Chinese population. Hereditas 10 25588301
2018 TCF4 and GRM8 gene polymorphisms and risk of schizophrenia in an Iranian population: a case-control study. Molecular biology reports 8 30288643
2018 Structural Basis for ( S)-3,4-Dicarboxyphenylglycine (DCPG) As a Potent and Subtype Selective Agonist of the mGlu8 Receptor. Journal of medicinal chemistry 8 30365309
2021 The effect of the mGlu8 receptor agonist, (S)-3,4-DCPG on acquisition and expression of morphine-induced conditioned place preference in male rats. Behavioral and brain functions : BBF 6 33612106
2011 Depression of release by mGluR8 alters Ca2+ dependence of release machinery. Cerebral cortex (New York, N.Y. : 1991) 6 21903594
2010 Selective activation of mGluR8 receptors modulates retinal ganglion cell light responses. Neuroscience 6 20096339
2018 Allosteric and Orthosteric Activators of mGluR8 Differentially Affect the Chemotherapeutic-Induced Human Neuroblastoma SH-SY5Y Cell Damage: The Impact of Cell Differentiation State. Basic & clinical pharmacology & toxicology 4 29753314
2016 Group III mGluR8 negatively modulates TRPA1. Neuroscience 4 27497709
2024 Rare CRHR2 and GRM8 variants identified as candidate factors associated with eating disorders in Japanese patients by whole exome sequencing. Heliyon 2 38644811
2016 Selective agonism of mGlu8 receptors by (S)-3,4-dicarboxyphenylglycine does not affect sleep stages in the rat. Pharmacological reports : PR 2 27914294
2025 Developmental differentiation of mouse inner ear neuron subpopulations resolved with a peripherin-promoter reporter within the Grm8 locus. Scientific reports 1 40133378
2025 Isoliquiritigenin as a Neuronal Radiation Mitigant: Mitigating Radiation-Induced Anhedonia Tendency Targeting Grik3/Grm8/Grin3a via Integrated Proteomics and AI-Driven Discovery. Pharmaceuticals (Basel, Switzerland) 1 41011178
2024 S-3,4-DCPG, a potent orthosteric agonist for the mGlu8 receptor, facilitates extinction and inhibits the reinstatement of morphine-induced conditioned place preference in male rats. Pharmacology, biochemistry, and behavior 1 38653345
2009 Effects of (RS)-3,4-DCPG, a mixed AMPA antagonist/mGluR8 agonist, on aggressive behavior in mice. Revista de psiquiatria y salud mental 1 23034312
2025 Red nucleus mGluR4 and mGluR8 inhibit nociception and the development of neuropathic pain by restraining the expressions of TNF-α and IL-1β. Neuropharmacology 0 40010564
2024 Thalamocortical mGlu8 Modulates Dorsal Thalamus Excitatory Transmission and Sensorimotor Activity. The Journal of neuroscience : the official journal of the Society for Neuroscience 0 38918065

Missed literature

Know a paper Affinage missed for GRM8? Flag it for the maintainers and the community.

No submissions yet.