Harman Patil (Editor)

Metabotropic glutamate receptor 2

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Species
  
Human

Entrez
  
2912

Human
  
Mouse

Ensembl
  
ENSG00000164082

Metabotropic glutamate receptor 2 wwwnaturecomneurojournalv16n4imagesnn3346

Aliases
  
GRM2, GPRC1B, MGLUR2, mGlu2, glutamate metabotropic receptor 2, mGluR2

External IDs
  
MGI: 1351339 HomoloGene: 20229 GeneCards: GRM2

Metabotropic glutamate receptor 2 is a protein that in humans is encoded by the GRM2 gene.

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 (this receptor) 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.

Role in hallucinogenesis

Many psychedelic drugs (e.g. LSD-25) produce their effects by binding to the oligomerized complexes of the 5HT2A and mGlu2 receptors. Lisuride acts preferentially or exclusively on the non-heteromerized 5HT2A receptors, which are not capable of inducing psychedelic effects. Due to this, lisuride is capable of reducing the hallucinogenic effects of these drugs through competitive agonistic activity (producing the effect of a silent-agonist in the presence of these drugs).

Strong agonists for either subunit of the 5HT2A-mGlu2R heterocomplex suppress signaling through the partner subunit and inverse agonists for either subunit potentiate the signaling through the partner subunit.

Ligands

The development of subtype-2-selective positive allosteric modulators (PAMs) experienced steady advance in recent years. mGluR2 potentiation is a new approach for the treatment of schizophrenia. On the other hand, antagonists and negative allosteric modulators of mGluR2/3 have potential as antidepressant drugs.

Agonists

  • Compound 1d (see reference)

    • PAMs

  • JNJ-46356479
  • JNJ-40411813
  • GSK-1331258
  • Imidazo[1,2-a]pyridines
  • 3-Aryl-5-phenoxymethyl-1,3-oxazolidin-2-ones
  • 3-(Imidazolyl methyl)-3-aza-bicyclo[3.1.0]hexan-6-yl)methyl ethers: potent, orally stable
  • BINA: potent; modest ago-allosteric modulator; robust in-vivo activity.
  • LY-487,379: devoid of orthosteric activity; along with related 3-pyridylmethylsulfonamides the first subtype-2-selective potentiator published (2003).

    • Antagonists

  • LY-341,495
  • MGS-0039
  • EGLU

    • NAMs

  • 7,8-dichloro-4-[3-(2-methylpyridin-4-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one and related compounds.
  • MNI-137 - 8-bromo-4-(2-cyanopyridin-4-yl)-1H-benzo[b][1,4]diazepin-2(3H)-one
  • RO4491533 - 4-[3-(2,6-dimethylpyridin-4-yl)phenyl]-7-methyl-8-trifluoromethyl-1,3-dihydrobenzo[b][1,4]diazepin-2-one

    • Protein–protein interactions

    The metabotropic glutamate receptor 2 is able to form a heteromeric complex with its isoform mGluR4. This heteromer exhibits a pharmacological profile distinct from the parent receptor monomers.

    References

    Metabotropic glutamate receptor 2 Wikipedia
    (Text) CC BY-SA