Metabotropic glutamate receptor 2

Metabotropic glutamate receptor 2
Glutamate receptor, metabotropic 2
Identifiers
Symbols GRM2; GLUR2; GPRC1B; MGLUR2; mGlu2
External IDs OMIM604099 MGI1351339 HomoloGene20229 GeneCards: 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_000839.3 NM_001160353.1
RefSeq (protein) NP_000830.2 NP_001153825.1
Location (UCSC) Chr 3:
51.74 – 51.75 Mb
Chr 9:
106.55 – 106.56 Mb
PubMed search [1] [2]

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

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.[2]

Contents

Ligands

PAMs

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]

Highly selective mGluR2 PAM (2010)[5], analog of BINA
  • GSK1331258[6]
  • Imidazo[1,2-a]pyridines[7]
  • 3-Aryl-5-phenoxymethyl-1,3-oxazolidin-2-ones[8]
  • 3-(Imidazolyl methyl)-3-aza-bicyclo[3.1.0]hexan-6-yl)methyl ethers: potent, orally stable[9]
  • BINA:[10][11] potent; modest ago-allosteric modulator; robust in-vivo activity.
  • LY487379:[12][13][14] devoid of orthosteric activity; along with related 3-pyridylmethylsulfonamides[15][16] the first subtype-2-selective potentiator published (2003).

See also

References

  1. ^ Flor PJ, Lindauer K, Puttner I, Ruegg D, Lukic S, Knopfel T, Kuhn R (Aug 1995). "Molecular cloning, functional expression and pharmacological characterization of the human metabotropic glutamate receptor type 2". Eur J Neurosci 7 (4): 622–9. doi:10.1111/j.1460-9568.1995.tb00666.x. PMID 7620613. 
  2. ^ a b "Entrez Gene: GRM2 glutamate receptor, metabotropic 2". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2912. 
  3. ^ PMID 19552508
  4. ^ Conn PJ, Jones CK (January 2009). "Promise of mGluR2/3 activators in psychiatry". Neuropsychopharmacology 34 (1): 248–9. doi:10.1038/npp.2008.156. PMC 2907744. PMID 19079073. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2907744. 
  5. ^ PMID 21155570
  6. ^ D'Alessandro PL, Corti C, Roth A, Ugolini A, Sava A, Montanari D, Bianchi F, Garland SL, Powney B, Koppe EL, Rocheville M, Osborne G, Perez P, de la Fuente J, De Los Frailes M, Smith PW, Branch C, Nash D, Watson SP (January 2010). "The identification of structurally novel, selective, orally bioavailable positive modulators of mGluR2". Bioorg. Med. Chem. Lett. 20 (2): 759–62. doi:10.1016/j.bmcl.2009.11.032. PMID 20005096. 
  7. ^ Tresadern G, Cid JM, Macdonald GJ, Vega JA, de Lucas AI, García A, Matesanz E, Linares ML, Oehlrich D, Lavreysen H, Biesmans I, Trabanco AA (January 2010). "Scaffold hopping from pyridones to imidazo[1,2-a]pyridines. New positive allosteric modulators of metabotropic glutamate 2 receptor". Bioorg. Med. Chem. Lett. 20 (1): 175–9. doi:10.1016/j.bmcl.2009.11.008. PMID 19932615. 
  8. ^ EJ Brnardic 2010
  9. ^ Zhang L, Rogers BN, Duplantier AJ et al. (2008). "3-(Imidazolyl methyl)-3-aza-bicyclo[3.1.0]hexan-6-yl)methyl ethers: a novel series of mGluR2 positive allosteric modulators". Bioorganic & medicinal chemistry letters 18 (20): 5493–6. doi:10.1016/j.bmcl.2008.09.026. PMID 18812259. 
  10. ^ Galici R, Jones CK, Hemstapat K et al. (2006). "Biphenyl-indanone A, a positive allosteric modulator of the metabotropic glutamate receptor subtype 2, has antipsychotic- and anxiolytic-like effects in mice". J. Pharmacol. Exp. Ther. 318 (1): 173–85. doi:10.1124/jpet.106.102046. PMID 16608916. 
  11. ^ Bonnefous C, Vernier JM, Hutchinson JH et al. (2005). "Biphenyl-indanones: allosteric potentiators of the metabotropic glutamate subtype 2 receptor". Bioorg. Med. Chem. Lett. 15 (19): 4354–8. doi:10.1016/j.bmcl.2005.06.062. PMID 16046122. 
  12. ^ Johnson MP, Baez M, Jagdmann GE et al. (2003). "Discovery of allosteric potentiators for the metabotropic glutamate 2 receptor: synthesis and subtype selectivity of N-(4-(2-methoxyphenoxy)phenyl)-N-(2,2,2- trifluoroethylsulfonyl)pyrid-3-ylmethylamine". J. Med. Chem. 46 (15): 3189–92. doi:10.1021/jm034015u. PMID 12852748. 
  13. ^ Johnson MP, Barda D, Britton TC et al. (2005). "Metabotropic glutamate 2 receptor potentiators: receptor modulation, frequency-dependent synaptic activity, and efficacy in preclinical anxiety and psychosis model(s)". Psychopharmacology (Berl.) 179 (1): 271–83. doi:10.1007/s00213-004-2099-9. PMID 15717213. 
  14. ^ Schaffhauser H, Rowe BA, Morales S et al. (2003). "Pharmacological characterization and identification of amino acids involved in the positive modulation of metabotropic glutamate receptor subtype 2". Mol. Pharmacol. 64 (4): 798–810. doi:10.1124/mol.64.4.798. PMID 14500736. 
  15. ^ Barda DA, Wang ZQ, Britton TC et al. (2004). "SAR study of a subtype selective allosteric potentiator of metabotropic glutamate 2 receptor, N-(4-phenoxyphenyl)-N-(3-pyridinylmethyl)ethanesulfonamide". Bioorg. Med. Chem. Lett. 14 (12): 3099–102. doi:10.1016/j.bmcl.2004.04.017. PMID 15149652. 
  16. ^ Pinkerton AB, Vernier JM, Schaffhauser H et al. (2004). "Phenyl-tetrazolyl acetophenones: discovery of positive allosteric potentiatiors for the metabotropic glutamate 2 receptor". J. Med. Chem. 47 (18): 4595–9. doi:10.1021/jm040088h. PMID 15317469. 

External links

Further reading

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


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