Metabotropic glutamate receptor 2

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Glutamate receptor, metabotropic 2, GluR2
Identifiers
Symbols GRM2 ; GLUR2; GPRC1B; MGLUR2; mGlu2
External IDs Template:OMIM5 HomoloGene: 20229
RNA expression pattern
File:PBB GE GRM2 208465 at tn.png
More reference expression data
Orthologs
Template:GNF Ortholog box
Species Human Mouse
Entrez n/a n/a
Ensembl n/a n/a
UniProt n/a n/a
RefSeq (mRNA) n/a n/a
RefSeq (protein) n/a n/a
Location (UCSC) n/a n/a
PubMed search n/a n/a

Glutamate receptor, metabotropic 2, GluR2, also known as GRM2, is a human gene.[1]

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.[1]

Ligands

Subtype-selective potentiators

Although a number of group-II-selective (GluR2/3) ligands are known, ligands displaying high selectivity, including subtype-selectivity over GluR3, are currently rare (2008). Examples of subtype-selective ligands are the following allosteric potentiators.[2] GluR2 potentiation is a new approach for the treatment of schizophrenia.

  • BINA:[3][4] potent potentiator; modest direct agonist; robust in-vivo activity [→formula]
  • LY487379:[5][6][7] devoid of orthosteric activity; along with related 3-pyridylmethylsulfonamides[8][9] the first subtype-2-selective potentiator published (2003).

See also

References

  1. ↑ 1.0 1.1 "Entrez Gene: GRM2 glutamate receptor, metabotropic 2".
  2. ↑ Rudd MT, McCauley JA (2005). "Positive allosteric modulators of the metabotropic glutamate receptor subtype 2 (mGluR2)". Curr Top Med Chem. 5 (9): 869–84. PMID 16178732.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.

Further reading

{{PBB_Further_reading | citations =

  • Flor PJ, Lindauer K, Püttner I; et al. (1995). "Molecular cloning, functional expression and pharmacological characterization of the human metabotropic glutamate receptor type 2". Eur. J. Neurosci. 7 (4): 622–9. PMID 7620613.
  • Scherer SW, Duvoisin RM, Kuhn R; et al. (1997). "Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q". Genomics. 31 (2): 230–3. doi:10.1006/geno.1996.0036. PMID 8824806.
  • Gomeza J, Mary S, Brabet I; et al. (1996). "Coupling of metabotropic glutamate receptors 2 and 4 to G alpha 15, G alpha 16, and chimeric G alpha q/i proteins: characterization of new antagonists". Mol. Pharmacol. 50 (4): 923–30. PMID 8863838.
  • Snow BE, Hall RA, Krumins AM; et al. (1998). "GTPase activating specificity of RGS12 and binding specificity of an alternatively spliced PDZ (PSD-95/Dlg/ZO-1) domain". J. Biol. Chem. 273 (28): 17749–55. PMID 9651375.
  • Malherbe P, Knoflach F, Broger C; et al. (2001). "Identification of essential residues involved in the glutamate binding pocket of the group II metabotropic glutamate receptor". Mol. Pharmacol. 60 (5): 944–54. PMID 11641422.
  • Martí SB, Cichon S, Propping P, Nöthen M (2002). "Human metabotropic glutamate receptor 2 gene (GRM2): chromosomal sublocalization (3p21.1-p21.2) and genomic organization". Am. J. Med. Genet. 114 (1): 12–4. PMID 11840499.
  • Krampfl K, Schlesinger F, Zörner A; et al. (2002). "Control of kinetic properties of GluR2 flop AMPA-type channels: impact of R/G nuclear editing". Eur. J. Neurosci. 15 (1): 51–62. PMID 11860506.
  • Dietrich D, Kral T, Clusmann H; et al. (2002). "Presynaptic group II metabotropic glutamate receptors reduce stimulated and spontaneous transmitter release in human dentate gyrus". Neuropharmacology. 42 (3): 297–305. PMID 11897108.
  • Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.
  • Kuwabara T, Hsieh J, Nakashima K; et al. (2004). "A small modulatory dsRNA specifies the fate of adult neural stem cells". Cell. 116 (6): 779–93. PMID 15035981.
  • Tang FR, Chia SC, Chen PM; et al. (2004). "Metabotropic glutamate receptor 2/3 in the hippocampus of patients with mesial temporal lobe epilepsy, and of rats and mice after pilocarpine-induced status epilepticus". Epilepsy Res. 59 (2–3): 167–80. doi:10.1016/j.eplepsyres.2004.04.002. PMID 15246118.
  • Anneser JM, Chahli C, Ince PG; et al. (2004). "Glial proliferation and metabotropic glutamate receptor expression in amyotrophic lateral sclerosis". J. Neuropathol. Exp. Neurol. 63 (8): 831–40. PMID 15330338.
  • Gerhard DS, Wagner L, Feingold EA; et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMID 15489334.
  • {{cite journal | author=Cube RV, Vernier JM, Hutchinson JH, et al. |title=3-(2-Ethoxy-4-{4-[3-hydroxy-2-methyl-4-(3-methylbutanoyl)phenoxy]butoxy}phenyl)propanoic acid: a brain penetrant allosteric potentiator at the metabotropic glutamate receptor 2 (mGluR2). |journal=Bioorg. Med. Chem. Lett. |volume=15 |issue= 9 |pages= 2389-93 |year= 2005 |pmid= 15837331 |doi= 10.1016/j.bmcl.2005.02.078 }}
  • Rodd ZA, McKinzie DL, Bell RL; et al. (2006). "The metabotropic glutamate 2/3 receptor agonist LY404039 reduces alcohol-seeking but not alcohol self-administration in alcohol-preferring (P) rats". Behav. Brain Res. 171 (2): 207–15. doi:10.1016/j.bbr.2006.03.032. PMID 16678921.

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