Metabotropic glutamate receptor 2

Metabotropic glutamate receptor 2

Glutamate receptor, metabotropic 2
Identifiers
Symbols GRM2; GLUR2; GPRC1B; MGLUR2; mGlu2
External IDs OMIM: GRM2 Gene
RNA expression pattern
PBB GE GRM2 208465 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 2912 108068
Ensembl ENSG00000164082 ENSMUSG00000023192
UniProt Q14416 Q14BI2
RefSeq (mRNA) NM_000839 NM_001160353
RefSeq (protein) NP_000830 NP_001153825
Location (UCSC) Chr 3:
51.74 – 51.75 Mb
Chr 9:
106.64 – 106.66 Mb
PubMed search [1] [2]

Metabotropic glutamate receptor 2 is a protein that in humans is encoded by the GRM2 gene.[1][2]

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.[2]

Ligands

The development of subtype-2-selective positive allosteric modulators (PAMs) experienced steady advance in recent years.[3] mGluR2 potentiation is a new approach for the treatment of schizophrenia.[4] On the other hand, antagonists and negative allosteric modulators of mGluR2/3 have potential as antidepressant drugs.[5][6][7][8]

PAMs

  • ADX-71149[10]
  • GSK1331258[11]
  • Imidazo[1,2-a]pyridines[12]
  • 3-Aryl-5-phenoxymethyl-1,3-oxazolidin-2-ones[13]
  • 3-(Imidazolyl methyl)-3-aza-bicyclo[3.1.0]hexan-6-yl)methyl ethers: potent, orally stable[14]
  • BINA:[15][16] potent; modest ago-allosteric modulator; robust in-vivo activity.
  • LY-487,379:[17][18][19] devoid of orthosteric activity; along with related 3-pyridylmethylsulfonamides[20][21] the first subtype-2-selective potentiator published (2003).

Antagonists

NAMs

  • 7,8-dichloro-4-[3-(2-methylpyridin-4-yl)phenyl]-1,3-dihydro-1,5-benzodiazepin-2-one and related compounds.[22]
  • MNI-137 - 8-bromo-4-(2-cyanopyridin-4-yl)-1H-benzo[b][1,4]diazepin-2(3H)-one[23]
  • RO4491533 - 4-[3-(2,6-dimethylpyridin-4-yl)phenyl]-7-methyl-8-trifluoromethyl-1,3-dihydrobenzo[b][1,4]diazepin-2-one[24]

See also

References

External links