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Gene Review

Grm3  -  glutamate receptor, metabotropic 3

Rattus norvegicus

Synonyms: Gprc1c, Metabotropic glutamate receptor 3, Mglur3, mGluR3
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Disease relevance of Grm3


Psychiatry related information on Grm3

  • 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].

High impact information on Grm3


Biological context of Grm3


Anatomical context of Grm3

  • Additionally, mGluR3 mRNA was found not only in neurones but also in putative glial cells [11].
  • 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 [12].
  • On immunoblot, the antibody reacted with both mGluR2 and mGluR3 in rat brain. mGluR2/3 immunoreactivity was expressed in cell bodies, dendrites, and axon terminals of Golgi cells, as well as in presumed glial processes [5].
  • Using the kindling model of temporal lobe seizures, we evaluated the ability of local hippocampal injections of mGluR1 antisense or mGluR3 antisense oligonucleotides to suppress receptor expression and alter hippocampal kindling [13].
  • These results show the important functional involvement of the limbic system together with the participation of components of different sensory systems in response to the activation of mGluR2 and mGluR3 with LY354740 and LY379268 [14].

Associations of Grm3 with chemical compounds

  • In this model, inhibition of caspase activation is mediated through the group II metabotropic glutamate receptor, mGluR3 [15].
  • Furthermore, we show that two mGluR3 agonists, the direct agonist (2R,4R)-4-aminopyrrolidine-2, 4-dicarboxylate (APDC) and N-acetyl-aspartyl-glutamate (NAAG) provide protection to neurons exposed to high glucose conditions, consistent with the concept that 2-PMPA neuroprotection is mediated by increased NAAG activity [15].
  • Protection against glucose-induced neuronal death by NAAG and GCP II inhibition is regulated by mGluR3 [15].
  • These data are consistent with the possibility that in primary cultures of cerebellar neurons, phosphoinositide responses may be predominantly mediated by mGluR1a, rather than mGluR5, and that cAMP inhibition involves preferentially mGluR4 and mGluR3 [16].
  • The effect of 100 microM tACPD was reproduced by 100 microM quisqualate, an agonist of mGluR2 and mGluR3 subtypes [17].

Physical interactions of Grm3

  • [(3)H]Quisqualic acid binding to mGluR1 required the presence of calcium (or magnesium) ions but not sodium or chloride ions while [(3)H]DCG-IV binding to mGluR3 was dependent upon both cations and anions [18].

Regulatory relationships of Grm3

  • (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) [19].
  • Both, group II mGluR-induced LTD and mGluR3-induced LTD were not abolished by mRNA/protein synthesis inhibition [20].
  • Furthermore, mGluR3-induced LTD was not inhibited by NMDA receptor antagonists or altered by L-type voltage-gated calcium channel blockers [20].

Other interactions of Grm3

  • Inhibition of GCP II or mGluR3 may represent a novel mechanism to treat neuronal degeneration under high-glucose conditions [15].
  • Both mGluR3 and mGluR4 inhibit the forskolin-stimulated accumulation of intracellular cAMP formation in response to agonist interaction [6].
  • In contrast, mGluR3 and mGluR5 were highly expressed at birth and decreased during maturation to adult levels of expression [21].
  • Similar decreases of mGluR7 mRNA expression in the VB and Po were found at all time points, while mGluR3 mRNA expression was bilaterally increased in the reticular thalamic nucleus (Rt) [22].
  • TGF-beta, a cytokine implicated in mGluR3-mediated neuroprotection, was also upregulated during the first 3 weeks after SE throughout the hippocampus [3].

Analytical, diagnostic and therapeutic context of Grm3

  • Quantitative densitometry showed high mGluR3 and 5 messenger RNA levels especially in the superficial dorsal horn at birth, however these levels decreased with age [23].
  • The examples we describe are that several different types of K(+) currents can be determined by patch clamp electrophysiology, of all the mGluRs only mGluR3 and 5 were detected by single cell RT-PCR, and that single cell Ca(2+) imaging shows that the mGluR5 receptor is functional [24].
  • Furthermore, reverse transcription-PCR, Northern blotting, and immunohistochemistry analyses indicated expression of class II mGluR3 in pinealocytes [25].


  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. Enhanced expression of metabotropic glutamate receptor 3 messenger RNA in the rat spinal cord during ultraviolet irradiation induced peripheral inflammation. Boxall, S.J., Berthele, A., Laurie, D.J., Sommer, B., Zieglgänsberger, W., Urban, L., Tölle, T.R. Neuroscience (1998) [Pubmed]
  3. Upregulation of metabotropic glutamate receptor subtype mGluR3 and mGluR5 in reactive astrocytes in a rat model of mesial temporal lobe epilepsy. Aronica, E., van Vliet, E.A., Mayboroda, O.A., Troost, D., da Silva, F.H., Gorter, J.A. Eur. J. Neurosci. (2000) [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. 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]
  6. Signal transduction, pharmacological properties, and expression patterns of two rat metabotropic glutamate receptors, mGluR3 and mGluR4. Tanabe, Y., Nomura, A., Masu, M., Shigemoto, R., Mizuno, N., Nakanishi, S. J. Neurosci. (1993) [Pubmed]
  7. The metabotropic glutamate receptor mGluR3 is critically required for hippocampal long-term depression and modulates long-term potentiation in the dentate gyrus of freely moving rats. Pöschel, B., Wroblewska, B., Heinemann, U., Manahan-Vaughan, D. Cereb. Cortex (2005) [Pubmed]
  8. Transcriptome analysis of frontal cortex in alcohol-preferring and nonpreferring rats. Worst, T.J., Tan, J.C., Robertson, D.J., Freeman, W.M., Hyytia, P., Kiianmaa, K., Vrana, K.E. J. Neurosci. Res. (2005) [Pubmed]
  9. 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]
  10. Differential negative coupling of type 3 metabotropic glutamate receptor to cyclic GMP levels in neurons and astrocytes. Wroblewska, B., Wegorzewska, I.N., Bzdega, T., Olszewski, R.T., Neale, J.H. J. Neurochem. (2006) [Pubmed]
  11. Differential distribution of metabotropic glutamate receptor subtype mRNAs in the thalamus of the rat. Lourenço Neto, F., Schadrack, J., Berthele, A., Zieglgänsberger, W., Tölle, T.R., Castro-Lopes, J.M. Brain Res. (2000) [Pubmed]
  12. 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]
  13. Inhibition of hippocampal kindling by metabotropic glutamate receptor antisense oligonucleotides. Greenwood, R.S., Fan, Z., McHugh, R., Meeker, R. Mol. Cell. Neurosci. (2000) [Pubmed]
  14. Group II selective metabotropic glutamate receptor agonists and local cerebral glucose use in the rat. Lam, A.G., Monn, J.A., Schoepp, D.D., Lodge, D., McCulloch, J. J. Cereb. Blood Flow Metab. (1999) [Pubmed]
  15. Protection against glucose-induced neuronal death by NAAG and GCP II inhibition is regulated by mGluR3. Berent-Spillson, A., Robinson, A.M., Golovoy, D., Slusher, B., Rojas, C., Russell, J.W. J. Neurochem. (2004) [Pubmed]
  16. 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]
  17. 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]
  18. Ion dependence of ligand binding to metabotropic glutamate receptors. Kuang, D., Hampson, D.R. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  19. 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]
  20. Group II mGluR-induced long term depression in the dentate gyrus in vivo is NMDA receptor-independent and does not require protein synthesis. Pöschel, B., Manahan-Vaughan, D. Neuropharmacology (2005) [Pubmed]
  21. Metabotropic glutamate receptors are differentially regulated during development. Catania, M.V., Landwehrmeyer, G.B., Testa, C.M., Standaert, D.G., Penney, J.B., Young, A.B. Neuroscience (1994) [Pubmed]
  22. Expression of metabotropic glutamate receptors mRNA in the thalamus and brainstem of monoarthritic rats. Lourenço Neto, F., Schadrack, J., Platzer, S., Zieglgänsberger, W., Tölle, T.R., Castro-Lopes, J.M. Brain Res. Mol. Brain Res. (2000) [Pubmed]
  23. Distribution and developmental changes in metabotropic glutamate receptor messenger RNA expression in the rat lumbar spinal cord. Berthele, A., Boxall, S.J., Urban, A., Anneser, J.M., Zieglgänsberger, W., Urban, L., Tölle, T.R. Brain Res. Dev. Brain Res. (1999) [Pubmed]
  24. Freshly isolated astrocyte (FIA) preparations: a useful single cell system for studying astrocyte properties. Kimelberg, H.K., Schools, G.P., Cai, Z., Zhou, M. J. Neurosci. Res. (2000) [Pubmed]
  25. Metabotropic glutamate receptors negatively regulate melatonin synthesis in rat pinealocytes. Yamada, H., Yatsushiro, S., Ishio, S., Hayashi, M., Nishi, T., Yamamoto, A., Futai, M., Yamaguchi, A., Moriyama, Y. J. Neurosci. (1998) [Pubmed]
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