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Gene Review

Grin1  -  glutamate receptor, ionotropic, N-methyl D...

Rattus norvegicus

Synonyms: GluN1, Glutamate receptor ionotropic, NMDA 1, N-methyl-D-aspartate receptor subunit NR1, NMD-R1, NMDAR1, ...
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Disease relevance of Grin1


Psychiatry related information on Grin1

  • Taking together, these findings suggested that NR2B containing NMDA receptor may be more involved with morphine reward rather than natural rewards, and that antagonism of NR2B may have a potential for the treatment of morphine abuse [6].
  • (2) Ifenprodil, an antagonist highly selective for NR2B subunit of the NMDA receptor, produced a dose-dependent reduction in CPP induced by morphine and novel environment, but not that by food consumption and social interaction [6].
  • The transient changes in NR1 and the NR2C subunit mRNA expressions in response to sensory deprivation are consistent with an active role for NMDA receptors in the appearance and development of the vestibular compensatory process [7].
  • The ability of these NMDA receptor antagonists to disrupt the prepulse inhibition (PPI) of the startle response and to alter locomotor activity was also studied [8].
  • The results show that chronic intraventricular infusion of the NMDA receptor antagonist D,L-2-amino-5-phosphonopentanoic acid (D,L-AP5) caused an impairment of spatial but not of visual discrimination learning in rats [9].

High impact information on Grin1

  • The rapid scaling induced by NMDAR mini blockade is mediated by increased synaptic expression of surface GluR1 and the transient incorporation of Ca2+-permeable AMPA receptors at synapses; both of these changes are implemented locally within dendrites and require dendritic protein synthesis [10].
  • These results indicate that NMDAR signaling during miniature synaptic transmission serves to stabilize synaptic function through active suppression of dendritic protein synthesis [10].
  • Consequently, the degree of astrocytic coverage of neurons governs the level of glycine site occupancy on the NMDA receptor, thereby affecting their availability for activation and thus the activity dependence of long-term synaptic changes [11].
  • Glia-derived D-serine controls NMDA receptor activity and synaptic memory [11].
  • (2006) show that D-serine released by astrocytes, a type of glial cell in the brain, promotes NMDA receptor activity at synapses in the hypothalamus [12].

Chemical compound and disease context of Grin1


Biological context of Grin1


Anatomical context of Grin1


Associations of Grin1 with chemical compounds

  • Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits [1].
  • Moreover, NR1/NR3A or -3B receptors form relatively Ca2+-impermeable cation channels that are resistant to Mg2+, MK-801, memantine and competitive antagonists [1].
  • Each cysteine residue in the NMDAR1 (NR1) subunit and each conserved NMDAR2 (NR2) cysteine residue in a prototypical subunit (NR2B) was tested for its role in redox modulation [24].
  • Thus, these striatal cell populations express different NMDAR-subunit mRNA phenotypes and therefore are likely to display NMDA channels with distinct pharmacological and physiological properties [19].
  • Fourteen glutamate receptor subunits were studied: GluR1-4 (including flip and flop variants), GluR5-7, KA1&2, NR1, and NR2A-D [23].

Physical interactions of Grin1


Enzymatic interactions of Grin1


Co-localisations of Grin1

  • BDNF was preferentially colocalized with glutamatergic markers VGLUT1 and NR1 ( approximately 30% each) [31].
  • The majority of NMDA receptor clusters were colocalized with the postsynaptic density proteins PSD-95, PSD-93, and SAP 102 [32].
  • However, after ischemia-induced neuronal death in these regions, double immunohistochemical labeling revealed that NR2B subunits colocalized with the astrocyte marker glial fibrillary acid protein and with NR1 subunits that are required for functional NMDA receptors [33].
  • Calretinin co-localizes with the NMDA receptor subunit NR1 in cholinergic amacrine cells of the rat retina [34].

Regulatory relationships of Grin1


Other interactions of Grin1

  • In the cerebellum, in contrast to staining with NR1 antibody, Purkinje cell staining with NR2A/B antibody was low, indicating that these neurons may lack functional NMDA receptors [20].
  • For the periaqueductal gray, prominent mRNAs were GluR-A, -B, and NR1 [22].
  • The percentage of GnRH neurons that double-labeled with NMDA-R1 was 2% in prepubertal rats and 3% in pubertal rats; this increased to 19% in postpubertal rats [3].
  • 4. Patches from these cells also contained 'low-conductance' NMDAR channels, with features characteristic of NR2D subunit-containing receptors [39].
  • TrkB was also relatively highly colocalized with VGLUT1 and NR1 ( approximately 20% each) but was additionally highly colocalized with GABAergic markers GAD-65 ( approximately 20%) and gamma2 ( approximately 30%) [31].

Analytical, diagnostic and therapeutic context of Grin1

  • We studied the expression of NMDA receptor subunits in neurochemically identified striatal neurons of adult rats by in situ hybridization histochemistry using a double-labeling technique [19].
  • Sodium deoxycholate at pH 9.0 solubilized about 35% of the receptor, which was intact based on co-immunoprecipitation of NR1 and NR2 subunits and chemical cross-linking of the solubilized receptor [40].
  • With the goal to determine quantitatively the subunit composition of cortical NMDA receptors, we used the monoclonal antibody to NR1 and polyclonal antibodies against the NR2A and NR2B subunits to perform immunoprecipitations of receptor subunits from solubilized adult rat cortical membranes [41].
  • 3. Single channel measurements in outside-out patches combined with RT-PCR on the same cell showed that NMDA-R channels from these neurones had main single channel conductance levels of 42 pS in 2 mM Ca2+ and 49 pS in 1 mM Ca2+ [42].
  • In the present study we investigated the modulation of hypothalamic NMDA receptor-mediated currents by cyclic AMP-dependent protein kinase (PKA) using the two-electrode voltage-clamp technique in XENOPUS: oocytes injected with rat hypothalamic mRNA [43].


  1. Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits. Chatterton, J.E., Awobuluyi, M., Premkumar, L.S., Takahashi, H., Talantova, M., Shin, Y., Cui, J., Tu, S., Sevarino, K.A., Nakanishi, N., Tong, G., Lipton, S.A., Zhang, D. Nature (2002) [Pubmed]
  2. Brain-derived neurotrophic factor and basic fibroblast growth factor downregulate NMDA receptor function in cerebellar granule cells. Brandoli, C., Sanna, A., De Bernardi, M.A., Follesa, P., Brooker, G., Mocchetti, I. J. Neurosci. (1998) [Pubmed]
  3. Gonadotropin-releasing hormone and NMDA receptor gene expression and colocalization change during puberty in female rats. Gore, A.C., Wu, T.J., Rosenberg, J.J., Roberts, J.L. J. Neurosci. (1996) [Pubmed]
  4. Transcription of the NR1 subunit of the N-methyl-D-aspartate receptor is down-regulated by excitotoxic stimulation and cerebral ischemia. Gascón, S., Deogracias, R., Sobrado, M., Roda, J.M., Renart, J., Rodríguez-Peña, A., Díaz-Guerra, M. J. Biol. Chem. (2005) [Pubmed]
  5. Changes in protein tyrosine phosphorylation in the rat brain after cerebral ischemia in a model of ischemic tolerance. Shamloo, M., Wieloch, T. J. Cereb. Blood Flow Metab. (1999) [Pubmed]
  6. The role of NR2B containing NMDA receptor in place preference conditioned with morphine and natural reinforcers in rats. Ma, Y.Y., Guo, C.Y., Yu, P., Lee, D.Y., Han, J.S., Cui, C.L. Exp. Neurol. (2006) [Pubmed]
  7. Regulation of NMDA receptor subunit mRNA expression in the guinea pig vestibular nuclei following unilateral labyrinthectomy. Sans, N., Sans, A., Raymond, J. Eur. J. Neurosci. (1997) [Pubmed]
  8. Substitution for PCP, disruption of prepulse inhibition and hyperactivity induced by N-methyl-D-aspartate receptor antagonists: preferential involvement of the NR2B rather than NR2A subunit. Chaperon, F., Müller, W., Auberson, Y.P., Tricklebank, M.D., Neijt, H.C. Behavioural pharmacology. (2003) [Pubmed]
  9. Synaptic plasticity and learning: selective impairment of learning rats and blockade of long-term potentiation in vivo by the N-methyl-D-aspartate receptor antagonist AP5. Morris, R.G. J. Neurosci. (1989) [Pubmed]
  10. Miniature neurotransmission stabilizes synaptic function via tonic suppression of local dendritic protein synthesis. Sutton, M.A., Ito, H.T., Cressy, P., Kempf, C., Woo, J.C., Schuman, E.M. Cell (2006) [Pubmed]
  11. Glia-derived D-serine controls NMDA receptor activity and synaptic memory. Panatier, A., Theodosis, D.T., Mothet, J.P., Touquet, B., Pollegioni, L., Poulain, D.A., Oliet, S.H. Cell (2006) [Pubmed]
  12. Astrocytes put down the broom and pick up the baton. Diamond, J.S. Cell (2006) [Pubmed]
  13. Increase in tyrosine phosphorylation of the NMDA receptor following the induction of status epilepticus. Huo, J.Z., Dykstra, C.M., Gurd, J.W. Neurosci. Lett. (2006) [Pubmed]
  14. Dopamine D1 receptor-dependent trafficking of striatal NMDA glutamate receptors to the postsynaptic membrane. Dunah, A.W., Standaert, D.G. J. Neurosci. (2001) [Pubmed]
  15. Expression of ionotropic glutamate receptor subunits in glial cells of the hippocampal CA1 area following transient forebrain ischemia. Gottlieb, M., Matute, C. J. Cereb. Blood Flow Metab. (1997) [Pubmed]
  16. Permeant ion regulation of N-methyl-D-aspartate receptor channel block by Mg(2+). Antonov, S.M., Johnson, J.W. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  17. Thermal hyperalgesia in association with the development of morphine tolerance in rats: roles of excitatory amino acid receptors and protein kinase C. Mao, J., Price, D.D., Mayer, D.J. J. Neurosci. (1994) [Pubmed]
  18. Kindling induces the long-lasting expression of a novel population of NMDA receptors in hippocampal region CA3. Kraus, J.E., Yeh, G.C., Bonhaus, D.W., Nadler, J.V., McNamara, J.O. J. Neurosci. (1994) [Pubmed]
  19. NMDA receptor subunit mRNA expression by projection neurons and interneurons in rat striatum. Landwehrmeyer, G.B., Standaert, D.G., Testa, C.M., Penney, J.B., Young, A.B. J. Neurosci. (1995) [Pubmed]
  20. The NMDA receptor subunits NR2A and NR2B show histological and ultrastructural localization patterns similar to those of NR1. Petralia, R.S., Wang, Y.X., Wenthold, R.J. J. Neurosci. (1994) [Pubmed]
  21. Bidirectional, experience-dependent regulation of N-methyl-D-aspartate receptor subunit composition in the rat visual cortex during postnatal development. Quinlan, E.M., Olstein, D.H., Bear, M.F. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  22. The differential expression of 16 NMDA and non-NMDA receptor subunits in the rat spinal cord and in periaqueductal gray. Tölle, T.R., Berthele, A., Zieglgänsberger, W., Seeburg, P.H., Wisden, W. J. Neurosci. (1993) [Pubmed]
  23. Expression of AMPA, kainate, and NMDA receptor subunits in cochlear and vestibular ganglia. Niedzielski, A.S., Wenthold, R.J. J. Neurosci. (1995) [Pubmed]
  24. Identification of two cysteine residues that are required for redox modulation of the NMDA subtype of glutamate receptor. Sullivan, J.M., Traynelis, S.F., Chen, H.S., Escobar, W., Heinemann, S.F., Lipton, S.A. Neuron (1994) [Pubmed]
  25. Cloning and characterization of chi-1: a developmentally regulated member of a novel class of the ionotropic glutamate receptor family. Ciabarra, A.M., Sullivan, J.M., Gahn, L.G., Pecht, G., Heinemann, S., Sevarino, K.A. J. Neurosci. (1995) [Pubmed]
  26. Apo-calmodulin binds with its C-terminal domain to the N-methyl-D-aspartate receptor NR1 C0 region. Akyol, Z., Bartos, J.A., Merrill, M.A., Faga, L.A., Jaren, O.R., Shea, M.A., Hell, J.W. J. Biol. Chem. (2004) [Pubmed]
  27. Morphine tolerance increases [3H]MK-801 binding affinity and constitutive neuronal nitric oxide synthase expression in rat spinal cord. Wong, C.S., Hsu, M.M., Chou, Y.Y., Tao, P.L., Tung, C.S. British journal of anaesthesia. (2000) [Pubmed]
  28. Hippocampal synaptic plasticity involves competition between Ca2+/calmodulin-dependent protein kinase II and postsynaptic density 95 for binding to the NR2A subunit of the NMDA receptor. Gardoni, F., Schrama, L.H., Kamal, A., Gispen, W.H., Cattabeni, F., Di Luca, M. J. Neurosci. (2001) [Pubmed]
  29. Comparison of binding at strychnine-sensitive (inhibitory glycine receptor) and strychnine-insensitive (N-methyl-D-aspartate receptor) glycine binding sites. Pullan, L.M., Powel, R.J. Neurosci. Lett. (1992) [Pubmed]
  30. Cyclic AMP-dependent protein kinase and protein kinase C phosphorylate N-methyl-D-aspartate receptors at different sites. Leonard, A.S., Hell, J.W. J. Biol. Chem. (1997) [Pubmed]
  31. Synaptic and extrasynaptic localization of brain-derived neurotrophic factor and the tyrosine kinase B receptor in cultured hippocampal neurons. Swanwick, C.C., Harrison, M.B., Kapur, J. J. Comp. Neurol. (2004) [Pubmed]
  32. Synaptic localization of NMDA receptor subunits in the rat retina. Fletcher, E.L., Hack, I., Brandstätter, J.H., Wässle, H. J. Comp. Neurol. (2000) [Pubmed]
  33. Functional NMDA receptor subtype 2B is expressed in astrocytes after ischemia in vivo and anoxia in vitro. Krebs, C., Fernandes, H.B., Sheldon, C., Raymond, L.A., Baimbridge, K.G. J. Neurosci. (2003) [Pubmed]
  34. Calretinin co-localizes with the NMDA receptor subunit NR1 in cholinergic amacrine cells of the rat retina. Araki, C.M., Hamassaki-Britto, D.E. Brain Res. (2000) [Pubmed]
  35. Brain-derived neurotrophic factor induces NMDA receptor subunit one phosphorylation via ERK and PKC in the rat spinal cord. Slack, S.E., Pezet, S., McMahon, S.B., Thompson, S.W., Malcangio, M. Eur. J. Neurosci. (2004) [Pubmed]
  36. Expression of NR1, NR2A-D, and NR3 subunits of the NMDA receptor in the cerebral cortex and olfactory bulb of adult rat. Sun, L., Shipley, M.T., Lidow, M.S. Synapse (2000) [Pubmed]
  37. Age and insulin-like growth factor-1 modulate N-methyl-D-aspartate receptor subtype expression in rats. Sonntag, W.E., Bennett, S.A., Khan, A.S., Thornton, P.L., Xu, X., Ingram, R.L., Brunso-Bechtold, J.K. Brain Res. Bull. (2000) [Pubmed]
  38. Protein kinase C modulates NMDA receptor trafficking and gating. Lan , J.Y., Skeberdis, V.A., Jover, T., Grooms, S.Y., Lin, Y., Araneda, R.C., Zheng, X., Bennett, M.V., Zukin, R.S. Nat. Neurosci. (2001) [Pubmed]
  39. Identification of subunits contributing to synaptic and extrasynaptic NMDA receptors in Golgi cells of the rat cerebellum. Misra, C., Brickley, S.G., Farrant, M., Cull-Candy, S.G. J. Physiol. (Lond.) (2000) [Pubmed]
  40. Relationship between N-methyl-D-aspartate receptor NR1 splice variants and NR2 subunits. Blahos, J., Wenthold, R.J. J. Biol. Chem. (1996) [Pubmed]
  41. The majority of N-methyl-D-aspartate receptor complexes in adult rat cerebral cortex contain at least three different subunits (NR1/NR2A/NR2B). Luo, J., Wang, Y., Yasuda, R.P., Dunah, A.W., Wolfe, B.B. Mol. Pharmacol. (1997) [Pubmed]
  42. Molecular determinants of NMDA receptor function in GABAergic neurones of rat forebrain. Plant, T., Schirra, C., Garaschuk, O., Rossier, J., Konnerth, A. J. Physiol. (Lond.) (1997) [Pubmed]
  43. Modulation of hypothalamic NMDA receptor function by cyclic AMP-dependent protein kinase and phosphatases. Nijholt, I., Blank, T., Liu, A., Kügler, H., Spiess, J. J. Neurochem. (2000) [Pubmed]
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