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Gene Review

Grm2  -  glutamate receptor, metabotropic 2

Mus musculus

Synonyms: 4930441L02Rik, Gprc1b, Metabotropic glutamate receptor 2, Mglur2, mGluR2, ...
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Disease relevance of Grm2


Psychiatry related information on Grm2

  • Moreover, monocular deprivation remained effective in mice lacking mGluR2, and receptor expression levels were unchanged during the critical period in wild-type mice, indicating that experience-dependent plasticity is independent of LTD induction in visual cortex [3].
  • 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 [4].
  • In the present study, male NMRI mice were injected with mGluR2/3 antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropyl-1-yl)-3-(xanth-9-yl)propanoic acid (LY-341495) 30 min before being placed into novel arenas for automatic motor activity recording (2-h sessions) [2].
  • The injection of AVP4-9 ameliorated PA task performance impairment induced by DCG-IV, an mGluR2/3 agonist [5].

High impact information on Grm2


Chemical compound and disease context of Grm2

  • High doses of AVP4-9 exacerbated the PA task performance impairment induced by LY341495 (an mGluR2/3 antagonist), and PMA injection (1 mug) also exacerbated the impairment induced by the antagonist [5].

Biological context of Grm2


Anatomical context of Grm2

  • In the present study, the pharmacology of mGluRs negatively coupled to AC in several neuronal types and in glial cells was compared with the pharmacology of mGluR2, -3, and -4 [8].
  • A small number of presynaptic axon terminals were labeled for mGluR2/3 immunoreactivity and formed asymmetrical synapses [10].
  • The mechanical injury produced by the needle insertion in the cerebral cortex also produced enhanced expression of mGluR5 and mGluR2/3 in activated astrocytes proximal to the area of neuronal injury [11].
  • Ca(L) channels were inhibited by the mGluR2/3 agonists. mGluR1/5 agonists accelerated and mGluR2/3 agonists suppressed the respiratory output, and correspondingly modified the hypoxic response of the respiratory center [12].
  • The quantitative comparison of receptor distributions demonstrates that mGluR1 alpha and mGluR5, but not mGluR2, are highly compartmentalised in different plasma membrane domains [13].

Associations of Grm2 with chemical compounds

  • This effect was mimicked by (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-I), a selective agonist of mGluR2/R3 receptors, but not by quisqualate at a concentration that stimulated inositol phosphate (InsP) synthesis, showing that mGluR1 and mGluR5 did not participate to this mechanism [14].
  • (S)-4C3HPG was, however, an agonist at mGluR2 with an EC50 of 21 +/- 4 microM for inhibition of forskolin-stimulated cyclic AMP formation in BHK cells expressing the mGluR2 [15].
  • Activation of mGluR2/3 reversibly depressed the fEPSP slopes in both the MPP and LPP, but no alterations were noted after PILO. mGluR8 activation selectively inhibited evoked responses in the LPP, but not in the MPP, and this level of inhibition did not change after PILO treatment [16].
  • PCCG-IV was significantly more potent and selective as an antagonist at mGluR2 compared with previously described mGluR2 antagonists, including alpha-methyl-4-carboxyphenylglycine [17].
  • 4. mGluR2/3 agonists (2S,1'R,2'R'3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV; 3 microM), (S)-4-carboxy-3-hydroxyphenylglycine (4C3HPG; 100-200 microM) and (S)-4-carboxyphenylglycine (4CPG; 300 microM) did not reduce NMDA current [18].

Physical interactions of Grm2

  • In a previous work, we demonstrated that striatal neurons in primary culture expressed a mGluR that is negatively coupled to AC and that has a pharmacology different from that of mGluR2 [8].

Other interactions of Grm2

  • These results suggest that mGluR2 or mGluR3 receptors suppress the activity of L-type Ca2+ channels by a mechanism involving Gi or G(o) proteins [14].
  • Several cDNAs coding for metabotropic glutamate receptors (mGluR1-7) have now been isolated. mGluR1 and -5 are positively coupled to phospholipase C, whereas mGluR2, -3, -4, -6, and -7 are negatively coupled to adenylyl cyclase (AC) when they are expressed in Chinese hamster ovary or baby hamster kidney cells [8].
  • Similar experiments revealed that cerebellar granule cells expressed mGluR2-like and mGluR4-like receptors [8].
  • Recent work has shown that the activation of mGluR2, a metabotropic glutamate receptor, localized at granule cell dendrites suppresses the GABA inhibition of the mitral cells and permits the formation of a specific olfactory memory that faithfully reflects the memory formed at mating [19].
  • By using immunofluorescence for metabotropic glutamate receptor 2 (mGluR2) and neurogranin as markers, we demonstrate the existence of five non-overlapping subsets of Golgi cells: about 65% are glycinergic/GABAergic and co-express both markers [20].

Analytical, diagnostic and therapeutic context of Grm2


  1. The metabotropic glutamate receptor 5 antagonist MPEP and the mGluR2 agonist LY379268 modify disease progression in a transgenic mouse model of Huntington's disease. Schiefer, J., Sprünken, A., Puls, C., Lüesse, H.G., Milkereit, A., Milkereit, E., Johann, V., Kosinski, C.M. Brain Res. (2004) [Pubmed]
  2. Habituation deficits induced by metabotropic glutamate receptors 2/3 receptor blockade in mice: reversal by antipsychotic drugs. Bespalov, A., Jongen-Rêlo, A.L., van Gaalen, M., Harich, S., Schoemaker, H., Gross, G. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  3. Experience-dependent plasticity without long-term depression by type 2 metabotropic glutamate receptors in developing visual cortex. Renger, J.J., Hartman, K.N., Tsuchimoto, Y., Yokoi, M., Nakanishi, S., Hensch, T.K. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  4. 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]
  5. Ameliorative and exacerbating effects of [pGlu(4),Cyt(6)]AVP((4-9)) on impairment of step-through passive avoidance task performance by group II metabotropic glutamate receptor-related drugs in mice. Sato, T., Ishida, T., Tanaka, K., Ohnishi, Y., Irifune, M., Mimura, T., Nishikawa, T. J. Pharmacol. Sci. (2005) [Pubmed]
  6. Impairment of hippocampal mossy fiber LTD in mice lacking mGluR2. Yokoi, M., Kobayashi, K., Manabe, T., Takahashi, T., Sakaguchi, I., Katsuura, G., Shigemoto, R., Ohishi, H., Nomura, S., Nakamura, K., Nakao, K., Katsuki, M., Nakanishi, S. Science (1996) [Pubmed]
  7. Enhanced cocaine responsiveness and impaired motor coordination in metabotropic glutamate receptor subtype 2 knockout mice. Morishima, Y., Miyakawa, T., Furuyashiki, T., Tanaka, Y., Mizuma, H., Nakanishi, S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  8. Pharmacological characterization of metabotropic glutamate receptors in several types of brain cells in primary cultures. Prézeau, L., Carrette, J., Helpap, B., Curry, K., Pin, J.P., Bockaert, J. Mol. Pharmacol. (1994) [Pubmed]
  9. MGS0039: a potent and selective group II metabotropic glutamate receptor antagonist with antidepressant-like activity. Chaki, S., Yoshikawa, R., Hirota, S., Shimazaki, T., Maeda, M., Kawashima, N., Yoshimizu, T., Yasuhara, A., Sakagami, K., Okuyama, S., Nakanishi, S., Nakazato, A. Neuropharmacology (2004) [Pubmed]
  10. Changes in subcellular localization of metabotropic glutamate receptor subtypes during postnatal development of mouse thalamus. Liu, X.B., Muñoz, A., Jones, E.G. J. Comp. Neurol. (1998) [Pubmed]
  11. Activated astrocytes in areas of kainate-induced neuronal injury upregulate the expression of the metabotropic glutamate receptors 2/3 and 5. Ferraguti, F., Corti, C., Valerio, E., Mion, S., Xuereb, J. Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. (2001) [Pubmed]
  12. Hypoxic modulation of L-type Ca(2+) channels in inspiratory brainstem neurones: intracellular signalling pathways and metabotropic glutamate receptors. Mironov, S.L., Richter, D.W. Brain Res. (2000) [Pubmed]
  13. Differential plasma membrane distribution of metabotropic glutamate receptors mGluR1 alpha, mGluR2 and mGluR5, relative to neurotransmitter release sites. Luján, R., Roberts, J.D., Shigemoto, R., Ohishi, H., Somogyi, P. J. Chem. Neuroanat. (1997) [Pubmed]
  14. The metabotropic glutamate receptor types 2/3 inhibit L-type calcium channels via a pertussis toxin-sensitive G-protein in cultured cerebellar granule cells. Chavis, P., Shinozaki, H., Bockaert, J., Fagni, L. J. Neurosci. (1994) [Pubmed]
  15. (S)-4-carboxy-3-hydroxyphenylglycine, an antagonist of metabotropic glutamate receptor (mGluR) 1a and an agonist of mGluR2, protects against audiogenic seizures in DBA/2 mice. Thomsen, C., Klitgaard, H., Sheardown, M., Jackson, H.C., Eskesen, K., Jacobsen, P., Treppendahl, S., Suzdak, P.D. J. Neurochem. (1994) [Pubmed]
  16. Medial perforant path inhibition mediated by mGluR7 is reduced after status epilepticus. Bough, K.J., Mott, D.D., Dingledine, R.J. J. Neurophysiol. (2004) [Pubmed]
  17. (2S,1'S,2'S,3'R)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine, a potent and selective antagonist of type 2 metabotropic glutamate receptors. Thomsen, C., Bruno, V., Nicoletti, F., Marinozzi, M., Pellicciari, R. Mol. Pharmacol. (1996) [Pubmed]
  18. Membrane-delimited modulation of NMDA currents by metabotropic glutamate receptor subtypes 1/5 in cultured mouse cortical neurons. Yu, S.P., Sensi, S.L., Canzoniero, L.M., Buisson, A., Choi, D.W. J. Physiol. (Lond.) (1997) [Pubmed]
  19. Synaptic mechanisms of olfactory recognition memory. Kaba, H., Nakanishi, S. Reviews in the neurosciences. (1995) [Pubmed]
  20. Heterogeneity of glycinergic and gabaergic interneurons in the granule cell layer of mouse cerebellum. Simat, M., Parpan, F., Fritschy, J.M. J. Comp. Neurol. (2007) [Pubmed]
  21. N-acetylaspartylglutamate activates cyclic AMP-coupled metabotropic glutamate receptors in cerebellar astrocytes. Wroblewska, B., Santi, M.R., Neale, J.H. Glia (1998) [Pubmed]
  22. The mGluR5 antagonist MPEP selectively inhibits the onset and maintenance of ethanol self-administration in C57BL/6J mice. Hodge, C.W., Miles, M.F., Sharko, A.C., Stevenson, R.A., Hillmann, J.R., Lepoutre, V., Besheer, J., Schroeder, J.P. Psychopharmacology (Berl.) (2006) [Pubmed]
  23. DCG-IV selectively attenuates rapidly triggered NMDA-induced neurotoxicity in cortical neurons. Buisson, A., Yu, S.P., Choi, D.W. Eur. J. Neurosci. (1996) [Pubmed]
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