Metabotropic glutamate receptor 7

Last updated
GRM7
7epc mGluR7 homodimer inactive.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases GRM7 , GLUR7, GPRC1G, MGLU7, MGLUR7, PPP1R87, glutamate metabotropic receptor 7, NEDSHBA
External IDs OMIM: 604101 MGI: 1351344 HomoloGene: 20233 GeneCards: GRM7
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000844
NM_181874
NM_181875

NM_177328
NM_001346640
NM_177970

RefSeq (protein)

NP_000835
NP_870989

NP_001333569
NP_796302

Location (UCSC) Chr 3: 6.77 – 7.74 Mb Chr 6: 110.62 – 111.54 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Metabotropic glutamate receptor 7 is a protein that in humans is encoded by the GRM7 gene. [5] [6] [7]

Contents

Function

L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Alternative splice variants of GRM8 have been described but their full-length nature has not been determined. [7]

Glutamate has lower affinity for mGluR7 than the other metabotropic glutamate receptors and it has been suggested that mGluR7 may have a regulatory role to dampen the effects of excessive glutamate levels. [8]

Ligands

Agonists

Antagonists

Negative allosteric modulators

Interactions

Metabotropic glutamate receptor 7 has been shown to interact with PICK1. [14]

Clinical

Mutations in both copies have been associated with developmental and epileptic encephalopathy, microcephaly, hypomyelination and cerebral atrophy. [15]

Related Research Articles

<span class="mw-page-title-main">Kainate receptor</span> Class of ionotropic glutamate receptors

Kainate receptors, or kainic acid receptors (KARs), are ionotropic receptors that respond to the neurotransmitter glutamate. They were first identified as a distinct receptor type through their selective activation by the agonist kainate, a drug first isolated from the algae Digenea simplex. They have been traditionally classified as a non-NMDA-type receptor, along with the AMPA receptor. KARs are less understood than AMPA and NMDA receptors, the other ionotropic glutamate receptors. Postsynaptic kainate receptors are involved in excitatory neurotransmission. Presynaptic kainate receptors have been implicated in inhibitory neurotransmission by modulating release of the inhibitory neurotransmitter GABA through a presynaptic mechanism.

<span class="mw-page-title-main">Metabotropic glutamate receptor</span> Type of glutamate receptor

The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs. Like all glutamate receptors, mGluRs bind with glutamate, an amino acid that functions as an excitatory neurotransmitter.

<span class="mw-page-title-main">Fenobam</span> Chemical compound

Fenobam is an imidazole derivative developed by McNeil Laboratories in the late 1970s as a novel anxiolytic drug with an at-the-time-unidentified molecular target in the brain. Subsequently, it was determined that fenobam acts as a potent and selective negative allosteric modulator of the metabotropic glutamate receptor subtype mGluR5, and it has been used as a lead compound for the development of a range of newer mGluR5 antagonists.

<span class="mw-page-title-main">PICK1</span> Protein-coding gene in the species Homo sapiens

Protein Interacting with C Kinase - 1 is a protein that in humans is encoded by the PICK1 gene.

<span class="mw-page-title-main">Metabotropic glutamate receptor 1</span> Mammalian protein found in humans

The glutamate receptor, metabotropic 1, also known as GRM1, is a human gene which encodes the metabotropic glutamate receptor 1 (mGluR1) protein.

<span class="mw-page-title-main">Metabotropic glutamate receptor 2</span> Mammalian protein found in humans

Metabotropic glutamate receptor 2 (mGluR2) is a protein that, in humans, is encoded by the GRM2 gene. mGluR2 is a G protein-coupled receptor (GPCR) that couples with the Gi alpha subunit. The receptor functions as an autoreceptor for glutamate, that upon activation, inhibits the emptying of vesicular contents at the presynaptic terminal of glutamatergic neurons.

<span class="mw-page-title-main">Metabotropic glutamate receptor 3</span> Mammalian protein found in humans

Metabotropic glutamate receptor 3 (mGluR3) is an inhibitory Gi/G0-coupled G-protein coupled receptor (GPCR) generally localized to presynaptic sites of neurons in classical circuits. However, in higher cortical circuits in primates, mGluR3 are localized post-synaptically, where they strengthen rather than weaken synaptic connectivity. In humans, mGluR3 is encoded by the GRM3 gene. Deficits in mGluR3 signaling have been linked to impaired cognition in humans, and to increased risk of schizophrenia, consistent with their expanding role in cortical evolution.

<span class="mw-page-title-main">Metabotropic glutamate receptor 4</span> Mammalian protein found in humans

Metabotropic glutamate receptor 4 is a protein that in humans is encoded by the GRM4 gene.

<span class="mw-page-title-main">Metabotropic glutamate receptor 5</span> Mammalian protein found in humans

Metabotropic glutamate receptor 5 is an excitatory Gq-coupled G protein-coupled receptor predominantly expressed on the postsynaptic sites of neurons. In humans, it is encoded by the GRM5 gene.

<span class="mw-page-title-main">Metabotropic glutamate receptor 6</span> Mammalian protein found in humans

Glutamate receptor, metabotropic 6, also known as GRM6 or mGluR6, is a protein which in humans is encoded by the GRM6 gene.

<span class="mw-page-title-main">Metabotropic glutamate receptor 8</span> Mammalian protein found in humans

Metabotropic glutamate receptor 8 is a protein that in humans is encoded by the GRM8 gene.

<span class="mw-page-title-main">LY-341495</span> Chemical compound

LY-341495 is a research drug developed by the pharmaceutical company Eli Lilly, which acts as a potent and selective orthosteric antagonist for the group II metabotropic glutamate receptors (mGluR2/3).

<span class="mw-page-title-main">AMN082</span> Chemical compound

AMN082 is a selective metabotropic glutamate receptor 7 (mGluR7) allosteric agonist. It mimics the effect of glutamate. AMN082 is the first selective mGluR7 agonist and has expanded the potential array of research opportunities on the effects of mGluR7 in the central nervous system.

<span class="mw-page-title-main">2-Methyl-6-(phenylethynyl)pyridine</span> Chemical compound

2-Methyl-6-(phenylethynyl)pyridine (MPEP) is a research drug which was one of the first compounds found to act as a selective antagonist for the metabotropic glutamate receptor subtype mGluR5. After being originally patented as a liquid crystal for LCDs, it was developed by the pharmaceutical company Novartis in the late 1990s. It was found to produce neuroprotective effects following acute brain injury in animal studies, although it was unclear whether these results were purely from mGluR5 blockade as it also acts as a weak NMDA antagonist, and as a positive allosteric modulator of another subtype mGlu4, and there is also evidence for a functional interaction between mGluR5 and NMDA receptors in the same populations of neurons. It was also shown to produce antidepressant and anxiolytic effects in animals, and to reduce the effects of morphine withdrawal, most likely due to direct interaction between mGluR5 and the μ-opioid receptor.

<span class="mw-page-title-main">PHCCC</span> Chemical compound

PHCCC is a research drug which acts as a glutamate receptor ligand, particularly being a positive allosteric modulator at the mGluR4 subtype, as well as an agonist at mGluR6. It has anxiolytic effects in animal studies. PHCCC and similar drugs have been suggested as novel treatments for Parkinson's disease.

<span class="mw-page-title-main">Ro01-6128</span> Chemical compound

Ro01-6128 is a drug used in scientific research, which acts as a selective positive allosteric modulator for the metabotropic glutamate receptor subtype mGluR1. It was derived by modification of a lead compound found via high-throughput screening, and was further developed to give the improved compound Ro67-4853.

<span class="mw-page-title-main">LY-379,268</span> Chemical compound

LY-379,268 is a drug that is used in neuroscience research, which acts as a potent and selective agonist for the group II metabotropic glutamate receptors (mGluR2/3).

<span class="mw-page-title-main">LY-487,379</span> Chemical compound

LY-487,379 is a drug used in scientific research that acts as a selective positive allosteric modulator for the metabotropic glutamate receptor group II subtype mGluR2. It is used to study the structure and function of this receptor subtype, and LY-487,379 along with various other mGluR2/3 agonists and positive modulators are being investigated as possible antipsychotic and anxiolytic drugs.

<span class="mw-page-title-main">AZD9272</span> Medication

AZD 9272 is a drug which acts as a selective antagonist for the metabotropic glutamate receptor subtype mGluR5. It was unsuccessful in human trials as an analgesic, but continues to be widely used in research especially as its radiolabelled forms.

<span class="mw-page-title-main">LSP2-9166</span> Chemical compound

LSP2-9166 is a drug which acts as a selective agonist for the group III metabotropic glutamate receptors, with a reasonably potent EC50 of 70nM at mGluR4 and 220nM at mGluR7, and weaker activity of 1380nM at mGluR6 and 4800nM at mGluR8. It has anticonvulsant effects in animal studies, and reduces self-administration of various addictive drugs.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000196277 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000056755 - Ensembl, May 2017
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  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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  7. 1 2 "Entrez Gene: GRM7 glutamate receptor, metabotropic 7".
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  11. Pelkey KA, Yuan X, Lavezzari G, Roche KW, McBain CJ (January 2007). "mGluR7 undergoes rapid internalization in response to activation by the allosteric agonist AMN082". Neuropharmacology. 52 (1): 108–117. doi:10.1016/j.neuropharm.2006.07.020. PMID   16914173. S2CID   23372757.
  12. Suzuki G, Tsukamoto N, Fushiki H, Kawagishi A, Nakamura M, Kurihara H, et al. (October 2007). "In vitro pharmacological characterization of novel isoxazolopyridone derivatives as allosteric metabotropic glutamate receptor 7 antagonists". The Journal of Pharmacology and Experimental Therapeutics. 323 (1): 147–156. doi:10.1124/jpet.107.124701. PMID   17609420. S2CID   10402176.
  13. Kalinichev M, Rouillier M, Girard F, Royer-Urios I, Bournique B, Finn T, et al. (March 2013). "ADX71743, a potent and selective negative allosteric modulator of metabotropic glutamate receptor 7: in vitro and in vivo characterization". The Journal of Pharmacology and Experimental Therapeutics. 344 (3): 624–636. doi:10.1124/jpet.112.200915. PMID   23257312. S2CID   5774001.
  14. Dev KK, Nakajima Y, Kitano J, Braithwaite SP, Henley JM, Nakanishi S (October 2000). "PICK1 interacts with and regulates PKC phosphorylation of mGLUR7". The Journal of Neuroscience. 20 (19): 7252–7257. doi:10.1523/JNEUROSCI.20-19-07252.2000. PMC   6772771 . PMID   11007882.
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Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.