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Gene Review

GRM1  -  glutamate receptor, metabotropic 1

Homo sapiens

Synonyms: GPRC1A, MGLU1, MGLUR1, Metabotropic glutamate receptor 1, PPP1R85, ...
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Disease relevance of GRM1


Psychiatry related information on GRM1

  • Therefore, group I mGluR dysfunction may be implicated in the pathogenesis of cognitive impairment and dementia in common form of DLB and pure AD [5].
  • These include mGluR1 antagonists in pain, mGluR5 antagonists in anxiety, pain and drug abuse and mGluR5 positive allosteric modulators in schizophrenia [6].
  • Genetic deletion of fragile X mental retardation protein (FMRP) has been shown to enhance mGluR-dependent long-term depression (LTD) [7].
  • CONCLUSIONS: These findings indicate that the expression of behavioral sensitization to cocaine-induced stimulation of locomotor activity may be modulated by group I mGluR antagonists (mGluR1 rather than mGluR5), but these effects occur at the dose levels that attenuate vertical activity [8].
  • These studies serve as a foundation for additional studies on underlying circuits, brain structures, and receptor subtypes involved in the anxiolytic-like actions of mGlu receptor active agents, and the design of future drugs for anxiety disorders in humans [9].

High impact information on GRM1

  • Physical mapping identified multiple tandem insertions of the transgene into intron 3 of Grm1 (encoding metabotropic glutamate receptor 1) with concomitant deletion of 70 kb of intronic sequence [1].
  • Although we did not detect its expression in normal mouse melanocytes, Grm1 was ectopically expressed in the melanomas from TG3 mice [1].
  • To assess whether this insertional mutagenesis event results in alteration of transcriptional regulation, we analyzed Grm1 and two flanking genes for aberrant expression in melanomas from TG3 mice [1].
  • We report here that (RS)-alpha-methyl-4-carboxyphenylglycine is a specific mGluR antagonist in the hippocampus and have used this compound to examine the nature of the involvement of mGluRs in LTP [10].
  • There is also circumstantial evidence that metabotropic glutamate receptors (mGluRs) may be involved in LTP because the specific mGluR agonist aminocyclopentane dicarboxylate can augment tetanus-induced LTP2 and, under certain circumstances, can itself induce a slow-onset potentiation [10].

Chemical compound and disease context of GRM1


Biological context of GRM1


Anatomical context of GRM1


Associations of GRM1 with chemical compounds


Regulatory relationships of GRM1

  • LY354740 inhibition of forskolin-stimulated cAMP formation in human mGlu2 receptor-expressing cells was blocked by competitive mGlu receptor antagonists, including (+)-alpha-methyl-4-carboxyphenylglycine (MCPG) and LY307452 ((2S,4S)-2-amino-4-(4,4-diphenylbut-1-yl)-pentane-1,5-dioic acid) [25].
  • Single-cell intracellular calcium ([Ca2+]i) recordings indicated that glutamate evokes a non-oscillatory and oscillatory [Ca2+]i response in mGluR1-expressing and mGluR5-expressing cells, respectively [26].
  • The palmitoylated, endogenously expressed G protein alpha-subunit alpha q could be immunoprecipitated from [3H]palmitate-labelled BHK cells expressing mGluR1 alpha using a specific antipeptide antibody, but in the same cell lysates no detectable [3H]palmitate-labelled mGluR1 alpha was found [27].
  • These data show that selective mGluR agonists that initiate signal-transduction events can regulate APP processing in bona fide primary neurons and transfected cells [28].
  • However, although PLD activation with CSA (100 microM) was highly effective at suppressing group I mGluR-mediated induction of burst prolongation, CSA application in the presence of chelerythrine was no longer effective and resulted in the expression of persistent ictaform bursts [29].

Other interactions of GRM1

  • Agonists acting on group II mGlu receptors (mGlu2, mGlu3) to reduce glutamate release are anticonvulsant, e.g., 2R,4R-aminopyrrolidine-2,4-dicarboxylate [(2R,4R)-APDC], (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740), and (-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268) [2].
  • Among the human group III mGlu receptors, the most potent inhibition of L-2-amino-4-phosphonobutyric acid (L-AP4) responses was seen for LY341495 at mGlu8, with an IC50 of 0.17 microM [30].
  • [3H]LY341495 binding to mGlu6, 7a and 8a was displaceable by compounds which interact functionally with group III mGlu receptors [31].
  • Gene-specific PCR using primers designed against human sequences indicates expression for all GluR, mGluR, and non-vesicular transporter subunits for which we probed [32].
  • Glutamate-induced decreases in brain endothelial barrier function and phosphorylated VASP were significantly attenuated by pretreatment of human brain endothelia with selective mGluR antagonists [21].

Analytical, diagnostic and therapeutic context of GRM1

  • Effects of mGluR and GABA(B) R agonists on insulin secretion were determined by radioimmunoassays and enzyme-linked immunoadsorbent assays (ELISAs) [33].
  • Western blot analysis demonstrated mGluR expression in both rat and human leptomeningeal tissues [34].
  • Studies in animal models of kindling reveal some efficacy of mGlu receptor ligands against fully kindled limbic seizures [2].
  • Transport of mGluR peripherally was investigated by vagal ligation, followed by immunohistochemistry [35].
  • Quantification of glutamate-induced mGluR1 splice variant internalization provided by enzyme-linked immunosorbent assay and confirmed by immunofluorescent microscopy indicated that each splice variant underwent rapid internalization, which was strongly inhibited by coexpression of dominant-negative mutant (DNM) arrestin or dynamin [36].


  1. Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia. Pollock, P.M., Cohen-Solal, K., Sood, R., Namkoong, J., Martino, J.J., Koganti, A., Zhu, H., Robbins, C., Makalowska, I., Shin, S.S., Marin, Y., Roberts, K.G., Yudt, L.M., Chen, A., Cheng, J., Incao, A., Pinkett, H.W., Graham, C.L., Dunn, K., Crespo-Carbone, S.M., Mackason, K.R., Ryan, K.B., Sinsimer, D., Goydos, J., Reuhl, K.R., Eckhaus, M., Meltzer, P.S., Pavan, W.J., Trent, J.M., Chen, S. Nat. Genet. (2003) [Pubmed]
  2. Glutamate metabotropic receptors as targets for drug therapy in epilepsy. Moldrich, R.X., Chapman, A.G., De Sarro, G., Meldrum, B.S. Eur. J. Pharmacol. (2003) [Pubmed]
  3. An influence of ligands of metabotropic glutamate receptor subtypes on parkinsonian-like symptoms and the striatopallidal pathway in rats. Ossowska, K., Konieczny, J., Wardas, J., Pietraszek, M., Kuter, K., Wolfarth, S., Pilc, A. Amino Acids (2007) [Pubmed]
  4. Among the twenty classical L-amino acids, only glutamate directly activates metabotropic glutamate receptors. Frauli, M., Neuville, P., Vol, C., Pin, J.P., Prézeau, L. Neuropharmacology (2006) [Pubmed]
  5. Impaired metabotropic glutamate receptor/phospholipase C signaling pathway in the cerebral cortex in Alzheimer's disease and dementia with Lewy bodies correlates with stage of Alzheimer's-disease-related changes. Albasanz, J.L., Dalfó, E., Ferrer, I., Martín, M. Neurobiol. Dis. (2005) [Pubmed]
  6. Ionotropic and metabotropic glutamate receptor structure and pharmacology. Kew, J.N., Kemp, J.A. Psychopharmacology (Berl.) (2005) [Pubmed]
  7. Dynamic translational and proteasomal regulation of fragile X mental retardation protein controls mGluR-dependent long-term depression. Hou, L., Antion, M.D., Hu, D., Spencer, C.M., Paylor, R., Klann, E. Neuron (2006) [Pubmed]
  8. Effects of group I metabotropic glutamate receptor antagonists on the behavioral sensitization to motor effects of cocaine in rats. Dravolina, O.A., Danysz, W., Bespalov, A.Y. Psychopharmacology (Berl.) (2006) [Pubmed]
  9. Anxiolytic-like activity of the mGLU2/3 receptor agonist LY354740 in the elevated plus maze test is disrupted in metabotropic glutamate receptor 2 and 3 knock-out mice. Linden, A.M., Shannon, H., Baez, M., Yu, J.L., Koester, A., Schoepp, D.D. Psychopharmacology (Berl.) (2005) [Pubmed]
  10. Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors. Bashir, Z.I., Bortolotto, Z.A., Davies, C.H., Berretta, N., Irving, A.J., Seal, A.J., Henley, J.M., Jane, D.E., Watkins, J.C., Collingridge, G.L. Nature (1993) [Pubmed]
  11. Expression and functional role of mGluR3 and mGluR5 in human astrocytes and glioma cells: opposite regulation of glutamate transporter proteins. Aronica, E., Gorter, J.A., Ijlst-Keizers, H., Rozemuller, A.J., Yankaya, B., Leenstra, S., Troost, D. Eur. J. Neurosci. (2003) [Pubmed]
  12. NAAG peptidase inhibition reduces locomotor activity and some stereotypes in the PCP model of schizophrenia via group II mGluR. Olszewski, R.T., Bukhari, N., Zhou, J., Kozikowski, A.P., Wroblewski, J.T., Shamimi-Noori, S., Wroblewska, B., Bzdega, T., Vicini, S., Barton, F.B., Neale, J.H. J. Neurochem. (2004) [Pubmed]
  13. Hippocampal gene expression analysis using the ORESTES methodology shows that homer 1a mRNA is upregulated in the acute period of the pilocarpine epilepsy model. Avedissian, M., Longo, B.M., Jaqueta, C.B., Schnabel, B., Paiva, P.B., Mello, L.E., Briones, M.R. Hippocampus (2007) [Pubmed]
  14. A comparison of two alternatively spliced forms of a metabotropic glutamate receptor coupled to phosphoinositide turnover. Pickering, D.S., Thomsen, C., Suzdak, P.D., Fletcher, E.J., Robitaille, R., Salter, M.W., MacDonald, J.F., Huang, X.P., Hampson, D.R. J. Neurochem. (1993) [Pubmed]
  15. LY354740: a metabotropic glutamate receptor agonist which ameliorates symptoms of nicotine withdrawal in rats. Helton, D.R., Tizzano, J.P., Monn, J.A., Schoepp, D.D., Kallman, M.J. Neuropharmacology (1997) [Pubmed]
  16. Assignment of the gene GRM1 coding for metabotropic glutamate receptor 1 to human chromosome band 6q24 by in situ hybridization. Ganesh, S., Amano, K., Yamakawa, K. Cytogenet. Cell Genet. (2000) [Pubmed]
  17. Metabotropic glutamate receptor subtypes as targets for neuroprotective drugs. Bruno, V., Battaglia, G., Copani, A., D'Onofrio, M., Di Iorio, P., De Blasi, A., Melchiorri, D., Flor, P.J., Nicoletti, F. J. Cereb. Blood Flow Metab. (2001) [Pubmed]
  18. Expression of functional mGlu5 metabotropic glutamate receptors in human melanocytes. Frati, C., Marchese, C., Fisichella, G., Copani, A., Nasca, M.R., Storto, M., Nicoletti, F. J. Cell. Physiol. (2000) [Pubmed]
  19. Functional metabotropic glutamate receptors are expressed in oligodendrocyte progenitor cells. Luyt, K., Varadi, A., Molnar, E. J. Neurochem. (2003) [Pubmed]
  20. The novel metabotropic glutamate receptor agonist 2R,4R-APDC potentiates stimulation of phosphoinositide hydrolysis in the rat hippocampus by 3,5-dihydroxyphenylglycine: evidence for a synergistic interaction between group 1 and group 2 receptors. Schoepp, D.D., Salhoff, C.R., Wright, R.A., Johnson, B.G., Burnett, J.P., Mayne, N.G., Belagaje, R., Wu, S., Monn, J.A. Neuropharmacology (1996) [Pubmed]
  21. Neutrophil-derived glutamate regulates vascular endothelial barrier function. Collard, C.D., Park, K.A., Montalto, M.C., Alapati, S., Buras, J.A., Stahl, G.L., Colgan, S.P. J. Biol. Chem. (2002) [Pubmed]
  22. Glial proliferation and metabotropic glutamate receptor expression in amyotrophic lateral sclerosis. Anneser, J.M., Chahli, C., Ince, P.G., Borasio, G.D., Shaw, P.J. J. Neuropathol. Exp. Neurol. (2004) [Pubmed]
  23. Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human huntington disease gene. Cha, J.H., Kosinski, C.M., Kerner, J.A., Alsdorf, S.A., Mangiarini, L., Davies, S.W., Penney, J.B., Bates, G.P., Young, A.B. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  24. BAY36-7620: a potent non-competitive mGlu1 receptor antagonist with inverse agonist activity. Carroll, F.Y., Stolle, A., Beart, P.M., Voerste, A., Brabet, I., Mauler, F., Joly, C., Antonicek, H., Bockaert, J., Müller, T., Pin, J.P., Prézeau, L. Mol. Pharmacol. (2001) [Pubmed]
  25. LY354740 is a potent and highly selective group II metabotropic glutamate receptor agonist in cells expressing human glutamate receptors. Schoepp, D.D., Johnson, B.G., Wright, R.A., Salhoff, C.R., Mayne, N.G., Wu, S., Cockerman, S.L., Burnett, J.P., Belegaje, R., Bleakman, D., Monn, J.A. Neuropharmacology (1997) [Pubmed]
  26. Glutamate receptors: brain function and signal transduction. Nakanishi, S., Nakajima, Y., Masu, M., Ueda, Y., Nakahara, K., Watanabe, D., Yamaguchi, S., Kawabata, S., Okada, M. Brain Res. Brain Res. Rev. (1998) [Pubmed]
  27. The metabotropic glutamate receptor mGluR4, but not mGluR1 alpha, is palmitoylated when expressed in BHK cells. Alaluf, S., Mulvihill, E.R., McIlhinney, R.A. J. Neurochem. (1995) [Pubmed]
  28. Amyloid precursor protein processing is stimulated by metabotropic glutamate receptors. Lee, R.K., Wurtman, R.J., Cox, A.J., Nitsch, R.M. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  29. Contrasting roles of protein kinase C in induction versus suppression of group I mGluR-mediated epileptogenesis in vitro. Cuellar, J.C., Griffith, E.L., Merlin, L.R. J. Neurophysiol. (2005) [Pubmed]
  30. LY341495 is a nanomolar potent and selective antagonist of group II metabotropic glutamate receptors. Kingston, A.E., Ornstein, P.L., Wright, R.A., Johnson, B.G., Mayne, N.G., Burnett, J.P., Belagaje, R., Wu, S., Schoepp, D.D. Neuropharmacology (1998) [Pubmed]
  31. Binding of [3H](2S,1'S,2'S)-2-(9-xanthylmethyl)-2-(2'-carboxycyclopropyl) glycine ([3H]LY341495) to cell membranes expressing recombinant human group III metabotropic glutamate receptor subtypes. Wright, R.A., Arnold, M.B., Wheeler, W.J., Ornstein, P.L., Schoepp, D.D. Naunyn Schmiedebergs Arch. Pharmacol. (2000) [Pubmed]
  32. Expression and sequences of genes encoding glutamate receptors and transporters in primate retina determined using 3'-end amplification polymerase chain reaction. Hanna, M.C., Calkins, D.J. Mol. Vis. (2006) [Pubmed]
  33. Metabotropic glutamate and GABA(B) receptors contribute to the modulation of glucose-stimulated insulin secretion in pancreatic beta cells. Brice, N.L., Varadi, A., Ashcroft, S.J., Molnar, E. Diabetologia (2002) [Pubmed]
  34. Expression of metabotropic glutamate receptors in rat meningeal and brain microvasculature and choroid plexus. Gillard, S.E., Tzaferis, J., Tsui, H.C., Kingston, A.E. J. Comp. Neurol. (2003) [Pubmed]
  35. Metabotropic glutamate receptors inhibit mechanosensitivity in vagal sensory neurons. Page, A.J., Young, R.L., Martin, C.M., Umaerus, M., O'Donnell, T.A., Cooper, N.J., Coldwell, J.R., Hulander, M., Mattsson, J.P., Lehmann, A., Blackshaw, L.A. Gastroenterology (2005) [Pubmed]
  36. Metabotropic glutamate receptor 1 internalization induced by muscarinic acetylcholine receptor activation: differential dependency of internalization of splice variants on nonvisual arrestins. Mundell, S.J., Matharu, A.L., Pula, G., Holman, D., Roberts, P.J., Kelly, E. Mol. Pharmacol. (2002) [Pubmed]
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