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Gene Review

Grm2  -  glutamate receptor, metabotropic 2

Rattus norvegicus

Synonyms: Gprc1b, Metabotropic glutamate receptor 2, Mglur2, mGluR2
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Disease relevance of Grm2

  • In pup and adult rats, status epilepticus induced a reduction in expression of mGluR2 mRNA in granule cells of the dentate gyrus [1].
  • Some cells in this layer (approximately 20% of the total), most likely both ganglion cells and displaced amacrine cells, were also labelled for mGluR2 and mGluR7 [2].
  • Cytoplasmic injection of mGluR2 cRNA into adult rat sympathetic neurons resulted in the expression of receptors that negatively coupled to N-type Ca2+ channels through a pertussis toxin-sensitive pathway [3].
  • APDC- and L-AP4-treated groups had higher expression levels of mGluR2/3 at the epicenter of injury on post contusion day 28; however, there was no difference in the amount of spared tissue between treatment groups [4].
  • Evaluation of the mGluR2/3 agonist LY379268 in rodent models of Parkinson's disease [5].

Psychiatry related information on Grm2

  • Previous studies indicate that agonists of the group II metabotropic glutamate receptors (mGluRs), mGluR2 and mGluR3, may provide a novel approach for the treatment of anxiety disorders and schizophrenia [6].
  • The mGluR5 antagonist MPEP, but not the mGluR2/3 agonist LY314582, augments PCP effects on prepulse inhibition and locomotor activity [7].
  • These results demonstrate that treatment with agonists to group II and III mGluRs following SCI affects mechanical responses, exploratory behavior, and mGluR2/3 expression without affecting the amount of tissue spared, suggesting that the level of mGluR expression after SCI may modulate nociceptive responses [4].

High impact information on Grm2

  • Our results indicate that mGluR2 in granule cells plays an important role in the persistent excitation of olfactory sensory transmission in the accessory olfactory bulb by relieving mitral cells from the GABA inhibition [8].
  • Using the DCG-IV agonist for mGluR2 in combination with slice patch-recording, we demonstrate that the granule cell mGluR2 presynaptically suppresses inhibitory GABA (gamma-aminobutyrate) transmission to the mitral cell [8].
  • Chimeras and deletions revealed that axon exclusion of mGluR2 versus axon targeting of mGluR7 is mediated by their 60 amino acid C-terminal cytoplasmic domains [9].
  • Coupling was restricted to specific transduction elements and effectors, since mGluR2 did not inhibit M channels and mGluR1 alpha had minimal effects on Ca2+ channels [3].
  • Immunohistochemical localization of metabotropic glutamate receptors, mGluR2 and mGluR3, in rat cerebellar cortex [10].

Chemical compound and disease context of Grm2


Biological context of Grm2

  • Comparison of the restricted mGluR2 and mGluR3 mRNA distributions with that of metabotropic ligand binding sites supports a possible presynaptic location for these receptors in the basal ganglia [12].
  • In hippocampal brain slices, BINA (1 microM) significantly potentiated the mGluR2/3 agonist-induced inhibition of excitatory synaptic transmission at the medial perforant path-dentate gyrus synapse [6].
  • We have identified a >70% reduction in basal cAMP levels following mGluR2 stimulation, which could lead to increased mGluR5 function via reduced PKA mediated phosphorylation and decreased desensitisation of mGluR5 [13].
  • (S)-4-Carboxyphenylglycine and (R,S)-alpha-methyl-4-carboxyphenylglycine competitively antagonized glutamate-induced inhibition of forskolin-stimulated cAMP-formation in BHK cells stably expressing mGluR2 with IC50 values of 577 +/- 74 microM and 340 +/- 59 microM, respectively [14].
  • 2. Application of a novel and potent mGluR2/mGluR3-specific agonist (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV, 0.1 microM) reversibly suppressed field excitatory postsynaptic potentials evoked by mossy fibre stimulation [15].

Anatomical context of Grm2

  • The subthalamic nucleus was the only other basal ganglia structure that expressed mGluR2 [12].
  • A further consistent feature in all species was labelling of astrocytes in the optic nerve/optic tract, superficial superior colliculus and brain at the collicular level with the antibody directed towards the Group II receptors, mGluR2 and mGluR3 [16].
  • (1R,2S,5S,6S)-2-Amino-6-fluoro-4-oxobicyclo[3.1. 0]hexane-2,6-dicarboxylic acid monohydrate ((+)-14, MGS0028) exhibited a remarkably high degree of agonist activity for mGluR2 (K(i) = 0.570 +/- 0.10 nM) and mGluR3 (K(i) = 2.07 +/- 0.40 nM) expressed in CHO cells but not mGluR4, 6, 7, 1a, or 5 expressed in CHO cells (K(i) = >100 000 nM) [17].
  • The dorsal motor nucleus of the vagus (DMN) contained mGluRla cell bodies, dendrites, and axonal fibers and light mGluR2/3 processes [18].
  • Both BrHI and MHI have weak agonist activity at mGluRs 4a and 7a expressed in stable BHK cell lines whereas neither compound had any activity on BHK cells expressing mGluR2 [19].

Associations of Grm2 with chemical compounds

  • In recombinant systems, BINA produced a robust and selective potentiation of the response of mGluR2 to glutamate with no effect on the glutamate response of other mGluR subtypes [6].
  • The behavioral effects of BINA were blocked by the mGluR2/3 antagonist (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495), suggesting that the in vivo effects of BINA are mediated by increased activation of mGluR2 [6].
  • The effect of 100 microM tACPD was reproduced by 100 microM quisqualate, an agonist of mGluR2 and mGluR3 subtypes [20].
  • These results suggest that LVA current can be enhanced by activation of mGluR2, by a mechanism that is G-protein dependent and may involve a protein tyrosine kinase step [21].
  • Two selective agonists of group 2 mGluRs, (2S,1's,2's)-2-(2'-carboxycyclopropyl)glycine and 4-carboxy-3-hydroxyphenylglycine, were totally ineffective in blocking CA3-CA1-evoked synaptic transmission, excluding the involvement of mGluR2/3 subtypes at this developmental stage [22].

Other interactions of Grm2


Analytical, diagnostic and therapeutic context of Grm2


  1. Status epilepticus-induced alterations in metabotropic glutamate receptor expression in young and adult rats. Aronica, E.M., Gorter, J.A., Paupard, M.C., Grooms, S.Y., Bennett, M.V., Zukin, R.S. J. Neurosci. (1997) [Pubmed]
  2. Expression of the mRNA of seven metabotropic glutamate receptors (mGluR1 to 7) in the rat retina. An in situ hybridization study on tissue sections and isolated cells. Hartveit, E., Brandstätter, J.H., Enz, R., Wässle, H. Eur. J. Neurosci. (1995) [Pubmed]
  3. Heterologous expression of metabotropic glutamate receptors in adult rat sympathetic neurons: subtype-specific coupling to ion channels. Ikeda, S.R., Lovinger, D.M., McCool, B.A., Lewis, D.L. Neuron (1995) [Pubmed]
  4. Role of group II and group III metabotropic glutamate receptors in spinal cord injury. Mills, C.D., Johnson, K.M., Hulsebosch, C.E. Exp. Neurol. (2002) [Pubmed]
  5. Evaluation of the mGluR2/3 agonist LY379268 in rodent models of Parkinson's disease. Murray, T.K., Messenger, M.J., Ward, M.A., Woodhouse, S., Osborne, D.J., Duty, S., O'Neill, M.J. Pharmacol. Biochem. Behav. (2002) [Pubmed]
  6. Biphenyl-indanone A, a positive allosteric modulator of the metabotropic glutamate receptor subtype 2, has antipsychotic- and anxiolytic-like effects in mice. Galici, R., Jones, C.K., Hemstapat, K., Nong, Y., Echemendia, N.G., Williams, L.C., de Paulis, T., Conn, P.J. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  7. The mGluR5 antagonist MPEP, but not the mGluR2/3 agonist LY314582, augments PCP effects on prepulse inhibition and locomotor activity. Henry, S.A., Lehmann-Masten, V., Gasparini, F., Geyer, M.A., Markou, A. Neuropharmacology (2002) [Pubmed]
  8. Role of a metabotropic glutamate receptor in synaptic modulation in the accessory olfactory bulb. Hayashi, Y., Momiyama, A., Takahashi, T., Ohishi, H., Ogawa-Meguro, R., Shigemoto, R., Mizuno, N., Nakanishi, S. Nature (1993) [Pubmed]
  9. Axon/dendrite targeting of metabotropic glutamate receptors by their cytoplasmic carboxy-terminal domains. Stowell, J.N., Craig, A.M. Neuron (1999) [Pubmed]
  10. Immunohistochemical localization of metabotropic glutamate receptors, mGluR2 and mGluR3, in rat cerebellar cortex. Ohishi, H., Ogawa-Meguro, R., Shigemoto, R., Kaneko, T., Nakanishi, S., Mizuno, N. Neuron (1994) [Pubmed]
  11. Toluene-induced locomotor activity is blocked by 6-hydroxydopamine lesions of the nucleus accumbens and the mGluR2/3 agonist LY379268. Riegel, A.C., Ali, S.F., French, E.D. Neuropsychopharmacology (2003) [Pubmed]
  12. Metabotropic glutamate receptor mRNA expression in the basal ganglia of the rat. Testa, C.M., Standaert, D.G., Young, A.B., Penney, J.B. J. Neurosci. (1994) [Pubmed]
  13. Metabotropic glutamate receptor signalling in perirhinal cortical neurons. Harris, S.L., Cho, K., Bashir, Z.I., Molnar, E. Mol. Cell. Neurosci. (2004) [Pubmed]
  14. Actions of phenylglycine analogs at subtypes of the metabotropic glutamate receptor family. Thomsen, C., Boel, E., Suzdak, P.D. Eur. J. Pharmacol. (1994) [Pubmed]
  15. Activation of metabotropic glutamate receptor type 2/3 suppresses transmission at rat hippocampal mossy fibre synapses. Kamiya, H., Shinozaki, H., Yamamoto, C. J. Physiol. (Lond.) (1996) [Pubmed]
  16. Distribution of metabotropic glutamate receptors in the superior colliculus of the adult rat, ferret and cat. Cirone, J., Sharp, C., Jeffery, G., Salt, T.E. Neuroscience (2002) [Pubmed]
  17. Synthesis, SARs, and pharmacological characterization of 2-amino-3 or 6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid derivatives as potent, selective, and orally active group II metabotropic glutamate receptor agonists. Nakazato, A., Kumagai, T., Sakagami, K., Yoshikawa, R., Suzuki, Y., Chaki, S., Ito, H., Taguchi, T., Nakanishi, S., Okuyama, S. J. Med. Chem. (2000) [Pubmed]
  18. Heterogeneity of metabotropic glutamate receptors in autonomic cell groups of the medulla oblongata of the rat. Hay, M., McKenzie, H., Lindsley, K., Dietz, N., Bradley, S.R., Conn, P.J., Hasser, E.M. J. Comp. Neurol. (1999) [Pubmed]
  19. 4-Methylhomoibotenic acid activates a novel metabotropic glutamate receptor coupled to phosphoinositide hydrolysis. Chung, D.S., Traynelis, S.F., Murphy, T.J., Conn, P.J. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
  20. Activation of multiple metabotropic glutamate receptor subtypes prevents NMDA-induced excitotoxicity in rat hippocampal slices. Pizzi, M., Consolandi, O., Memo, M., Spano, P.F. Eur. J. Neurosci. (1996) [Pubmed]
  21. Enhancement of low-voltage-activated calcium currents by group II metabotropic glutamate receptors in rat retinal ganglion cells. Robbins, J., Reynolds, A.M., Treseder, S., Davies, R. Mol. Cell. Neurosci. (2003) [Pubmed]
  22. Metabotropic glutamate receptors inhibiting excitatory synapses in the CA1 area of rat hippocampus. Manzoni, O., Bockaert, J. Eur. J. Neurosci. (1995) [Pubmed]
  23. Temporal and depolarization-induced changes in the absolute amounts of mRNAs encoding metabotropic glutamate receptors in cerebellar granule neurons in vitro. Santi, M.R., Ikonomovic, S., Wroblewski, J.T., Grayson, D.R. J. Neurochem. (1994) [Pubmed]
  24. Cannabinoids and dopamine receptors' action on calcium current in rat neurons. Vásquez, C., Navarro-Polanco, R., Hernández, G., Ruiz, J., Guerra, D.G., Baltazar, L.M., Huerta, M., Trujillo, X. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques. (2005) [Pubmed]
  25. Activation of the extracellular signal-regulated kinase 2 by metabotropic glutamate receptors. Ferraguti, F., Baldani-Guerra, B., Corsi, M., Nakanishi, S., Corti, C. Eur. J. Neurosci. (1999) [Pubmed]
  26. Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus. Shigemoto, R., Kinoshita, A., Wada, E., Nomura, S., Ohishi, H., Takada, M., Flor, P.J., Neki, A., Abe, T., Nakanishi, S., Mizuno, N. J. Neurosci. (1997) [Pubmed]
  27. Changes in mRNA for metabotropic glutamate receptors after transient cerebral ischaemia. Rosdahl, D., Seitzberg, D.A., Christensen, T., Balchen, T., Diemer, N.H. Neuroreport (1994) [Pubmed]
  28. Cyclosporine-A treatment inhibits the expression of metabotropic glutamate receptors in rat thymus. Rezzani, R., Corsetti, G., Rodella, L., Angoscini, P., Lonati, C., Bianchi, R. Acta Histochem. (2003) [Pubmed]
  29. Metabotropic glutamate receptor 2 modulates excitatory synaptic transmission in the rat globus pallidus. Poisik, O., Raju, D.V., Verreault, M., Rodriguez, A., Abeniyi, O.A., Conn, P.J., Smith, Y. Neuropharmacology (2005) [Pubmed]
  30. Group II and group III metabotropic glutamate receptors in the rat retina: distributions and developmental expression patterns. Koulen, P., Malitschek, B., Kuhn, R., Wässle, H., Brandstätter, J.H. Eur. J. Neurosci. (1996) [Pubmed]
  31. Metabotropic glutamate receptors mGluR2 and mGluR5 are expressed in two non-overlapping populations of Golgi cells in the rat cerebellum. Neki, A., Ohishi, H., Kaneko, T., Shigemoto, R., Nakanishi, S., Mizuno, N. Neuroscience (1996) [Pubmed]
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