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Grin3a  -  glutamate receptor, ionotropic, N-methyl-D...

Rattus norvegicus

Synonyms: GluN3A, Glutamate receptor chi-1, Glutamate receptor ionotropic, NMDA 3A, N-methyl-D-aspartate receptor, N-methyl-D-aspartate receptor subtype 3A, ...
 
 
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Disease relevance of Grin3a

  • In human embryonic kidney 293 cells expressing the D1R/NMDAR, complex costimulation of both D1R and NMDAR, but not individual receptor activation, promoted internalization, suggesting that development of dyskinesias might be related to agonist-mediated down-regulation of the D1R/NMDAR complex at corticostriatal synapses [1].
  • Detection of delta opioid receptor and N-methyl-D-aspartate receptor-like immunoreactivity in retinoic acid-differentiated neuroblastoma x glioma (NG108-15) cells [2].
  • CONCLUSION: This study is the first to show that NMDAr exists in the peripheral vasculature, and that homocysteine may act via NMDAr to increase intimal hyperplasia [3].
  • To study NMDAR structure and function, we have searched for peptide modulators of NR1 using random peptide bacteriophage libraries [4].
  • NR3A protein expression was initially observed in the first postnatal week and was predominantly localized to cell bodies in the ganglion cell layer [5].
 

Psychiatry related information on Grin3a

  • N-methyl-D-aspartate receptor (NMDAR) agonist quinolinic acid (QUIN)-induced excitotoxicity has been implicated in neurodegeneration and mimics Huntington's disease (HD) by the loss of medium-sized spiny projection neurons while sparing medium-sized aspiny interneurons in the striatum [6].
  • Local dopaminergic modulation of the motor activity induced by N-methyl-D-aspartate receptor stimulation in the ventral hippocampus [7].
  • Although phencyclidine is known as a N-methyl d-aspartate receptor antagonist (NMDA-R), the molecular events underlying the behavioral symptoms remain largely unknown [8].
  • Concurrent activation of hippocampal glycine and polyamine sites of the N-methyl-D-aspartate receptor synergistically reverses working memory deficits in rats [9].
  • N-methyl-D-aspartate receptor-dependent plasticity within a distributed corticostriatal network mediates appetitive instrumental learning [10].
 

High impact information on Grin3a

  • Here we report the cloning and characterization of the final member of the NMDAR family, NR3B, which shares high sequence homology with NR3A [11].
  • From in situ and immunocytochemical analyses, NR3B is expressed predominantly in motor neurons, whereas NR3A is more widely distributed [11].
  • Conventional heteromeric NMDARs composed of NR1 and NR2A-D subunits require dual agonists, glutamate and glycine, for activation [11].
  • Remarkably, when co-expressed in Xenopus oocytes, NR3A or NR3B co-assembles with NR1 to form excitatory glycine receptors that are unaffected by glutamate or NMDA, and inhibited by D-serine, a co-activator of conventional NMDARs [11].
  • Moreover, NR1/NR3A or -3B receptors form relatively Ca2+-impermeable cation channels that are resistant to Mg2+, MK-801, memantine and competitive antagonists [11].
 

Chemical compound and disease context of Grin3a

 

Biological context of Grin3a

  • Spatial and temporal regulation of RACK1 function and N-methyl-D-aspartate receptor activity through WD40 motif-mediated dimerization [17].
  • The results of this study demonstrate that NR3A is expressed, distributed, and associated with other subunits in a manner that supports its role in synaptic transmission throughout the rat brain, perhaps playing different roles during development [18].
  • Furthermore, ethanol inhibited a form of long-term potentiation induced by very high frequency stimulation that does not depend on N-methyl-D-aspartate receptor activation [19].
  • Specifically, our results reveal that the frequency of miniature excitatory postsynaptic currents is significantly reduced by 7-chloro-kynurenic acid (7-Cl KYNA), a NMDA-R glycine binding site antagonist, and glycine or d-serine reverses this effect [20].
  • All NMDAr subunits were expressed in the RAECs, and there was 92% to 100% similarity compared with rat NMDAr from the National Center for Biotechnology Information (NCBI) GenBank [3].
 

Anatomical context of Grin3a

 

Associations of Grin3a with chemical compounds

  • In striatal postsynaptic densities (PSD), the dopamine D1 receptor (D1R) is part of an oligomeric complex with the glutamate N-methyl-D-aspartate receptor (NMDAR), determining the strength of corticostriatal transmission [1].
  • In the CA1 region of rat hippocampal slices, ethanol partially inhibited N-methyl-d-aspartate receptor-mediated synaptic responses at concentrations up to 180 mM [19].
  • Ethanol did not occlude the effects of a low concentration of 2-amino-5-phosphonovalerate, an antagonist with less N-methyl-d-aspartate receptor subtype selectivity [19].
  • Recent studies indicate that ifenprodil and other NR2B-selective antagonists inhibit N-methyl-D-aspartate receptor-dependent long-term depression but not long-term potentiation [19].
  • For receptor protein expression, RAEC were incubated with different homocysteine concentrations and incubation times and also were treated with 50 microM homocysteine and/or preincubated with 50 microM dizocilpine MK-801, an NMDAr inhibitor [3].
 

Physical interactions of Grin3a

  • Since chi-1 did not alter the currents generated by non-NMDA subunits, this suggests that chi-1 may specifically interact with NMDA receptor subunits [25].
 

Regulatory relationships of Grin3a

  • NR2C and NR3 were expressed at levels which were approximately 15% of those of NR1 [26].
 

Other interactions of Grin3a

  • NR3A expression peaks between postnatal days 7 and 10 in the cortex, midbrain, and hippocampus and reaches higher maximal expression levels in these areas than in the olfactory bulb and cerebellum [18].
 

Analytical, diagnostic and therapeutic context of Grin3a

  • In situ hybridization experiments indicated that NMDAR-L mRNA was expressed in the developing rodent CNS [21].
  • We developed an antibody to NR3A and, using quantitative immunoblotting techniques, determined the degree of association between the NR3A subunit and the NR1 and NR2 subunits as well as changes in these associations during development [18].
  • Immunoprecipitation experiments with an anti-NR1 antibody demonstrated that the majority of NR3A is associated with NR1 in postnatal day 10 rat cortex (80 +/- 8%), decreasing by half (38 +/- 4%) in the adult rat cortex [18].
  • RNA was isolated from RAECs, and expression of all NMDAr subunits (NR1, 2A, 2B, 2C, and 2D) were examined by RT-PCR and sequencing [3].
  • NR1, NR2 and NR3 subunits were detected in myelin by immunohistochemistry and immunoprecipitation, indicating that all necessary subunits are present for the formation of functional NMDA receptors [27].

References

  1. Loss of synaptic D1 dopamine/N-methyl-D-aspartate glutamate receptor complexes in L-DOPA-induced dyskinesia in the rat. Fiorentini, C., Rizzetti, M.C., Busi, C., Bontempi, S., Collo, G., Spano, P., Missale, C. Mol. Pharmacol. (2006) [Pubmed]
  2. Detection of delta opioid receptor and N-methyl-D-aspartate receptor-like immunoreactivity in retinoic acid-differentiated neuroblastoma x glioma (NG108-15) cells. Beczkowska, I.W., Gracy, K.N., Pickel, V.M., Inturrisi, C.E. J. Neurosci. Res. (1997) [Pubmed]
  3. Identification of a homocysteine receptor in the peripheral endothelium and its role in proliferation. Chen, H., Fitzgerald, R., Brown, A.T., Qureshi, I., Breckenridge, J., Kazi, R., Wang, Y., Wu, Y., Zhang, X., Mukunyadzi, P., Eidt, J., Moursi, M.M. J. Vasc. Surg. (2005) [Pubmed]
  4. In vitro selection of peptides acting at a new site of NMDA glutamate receptors. Li, M., Yu, W., Chen, C.H., Cwirla, S., Whitehorn, E., Tate, E., Raab, R., Bremer, M., Dower, B. Nat. Biotechnol. (1996) [Pubmed]
  5. N-methyl-D-aspartate receptor subunit NR3A in the retina: developmental expression, cellular localization, and functional aspects. Sucher, N.J., Kohler, K., Tenneti, L., Wong, H.K., Gründer, T., Fauser, S., Wheeler-Schilling, T., Nakanishi, N., Lipton, S.A., Guenther, E. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  6. Characterization of striatal cultures with the effect of QUIN and NMDA. Kumar, U. Neurosci. Res. (2004) [Pubmed]
  7. Local dopaminergic modulation of the motor activity induced by N-methyl-D-aspartate receptor stimulation in the ventral hippocampus. Giménez-Llort, L., Wang, F.H., Ogren, S.O., Ferré, S. Neuropsychopharmacology (2002) [Pubmed]
  8. Phencyclidine-induced changes in rat cortical gene expression identified by microarray analysis: implications for schizophrenia. Kaiser, S., Foltz, L.A., George, C.A., Kirkwood, S.C., Bemis, K.G., Lin, X., Gelbert, L.M., Nisenbaum, L.K. Neurobiol. Dis. (2004) [Pubmed]
  9. Concurrent activation of hippocampal glycine and polyamine sites of the N-methyl-D-aspartate receptor synergistically reverses working memory deficits in rats. Kishi, A., Ohno, M., Watanabe, S. Neurosci. Lett. (1998) [Pubmed]
  10. N-methyl-D-aspartate receptor-dependent plasticity within a distributed corticostriatal network mediates appetitive instrumental learning. Baldwin, A.E., Holahan, M.R., Sadeghian, K., Kelley, A.E. Behav. Neurosci. (2000) [Pubmed]
  11. 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]
  12. Specific inhibition of N-methyl-D-aspartate receptor function in rat hippocampal neurons by L-phenylalanine at concentrations observed during phenylketonuria. Glushakov, A.V., Dennis, D.M., Morey, T.E., Sumners, C., Cucchiara, R.F., Seubert, C.N., Martynyuk, A.E. Mol. Psychiatry (2002) [Pubmed]
  13. D-cycloserine facilitates synaptic plasticity but impairs glutamatergic neurotransmission in rat hippocampal slices. Rouaud, E., Billard, J.M. Br. J. Pharmacol. (2003) [Pubmed]
  14. N-methyl-D-aspartate receptor blockade after status epilepticus protects against limbic brain damage but not against epilepsy in the kainate model of temporal lobe epilepsy. Brandt, C., Potschka, H., Löscher, W., Ebert, U. Neuroscience (2003) [Pubmed]
  15. Modulation of blood-brain barrier dysfunction and neurological deficits during acute experimental allergic encephalomyelitis by the N-methyl-D-aspartate receptor antagonist memantine. Paul, C., Bolton, C. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  16. Late N-methyl-D-aspartate receptor blockade rescues hippocampal neurons from excitotoxic stress and death after 4-aminopyridine-induced epilepsy. Ayala, G.X., Tapia, R. Eur. J. Neurosci. (2005) [Pubmed]
  17. Spatial and temporal regulation of RACK1 function and N-methyl-D-aspartate receptor activity through WD40 motif-mediated dimerization. Thornton, C., Tang, K.C., Phamluong, K., Luong, K., Vagts, A., Nikanjam, D., Yaka, R., Ron, D. J. Biol. Chem. (2004) [Pubmed]
  18. Association of NR3A with the N-methyl-D-aspartate receptor NR1 and NR2 subunits. Al-Hallaq, R.A., Jarabek, B.R., Fu, Z., Vicini, S., Wolfe, B.B., Yasuda, R.P. Mol. Pharmacol. (2002) [Pubmed]
  19. Acute effects of ethanol on hippocampal long-term potentiation and long-term depression are mediated by different mechanisms. Izumi, Y., Nagashima, K., Murayama, K., Zorumski, C.F. Neuroscience (2005) [Pubmed]
  20. Glycine Binding Sites of Presynaptic NMDA Receptors May Tonically Regulate Glutamate Release in the Rat Visual Cortex. Li, Y.H., Han, T.Z. J. Neurophysiol. (2007) [Pubmed]
  21. Developmental and regional expression pattern of a novel NMDA receptor-like subunit (NMDAR-L) in the rodent brain. Sucher, N.J., Akbarian, S., Chi, C.L., Leclerc, C.L., Awobuluyi, M., Deitcher, D.L., Wu, M.K., Yuan, J.P., Jones, E.G., Lipton, S.A. J. Neurosci. (1995) [Pubmed]
  22. Attenuated lesion-induced N-methyl-D-aspartate receptor (NMDAR) plasticity in the dentate gyrus of aged rats following perforant path lesions. Adams, M.M., Gazzaley, A.H., Morrison, J.H. Exp. Neurol. (2001) [Pubmed]
  23. Dark-rearing decreases NR2A N-methyl-D-aspartate receptor subunit in all visual cortical layers. Tongiorgi, E., Ferrero, F., Cattaneo, A., Domenici, L. Neuroscience (2003) [Pubmed]
  24. Turnover analysis of N-methyl-D-aspartate receptor subunit NR1 protein in PC12 cells. Vazhappilly, R., Sucher, N.J. Neurosci. Lett. (2002) [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. 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]
  27. NMDA receptors mediate calcium accumulation in myelin during chemical ischaemia. Micu, I., Jiang, Q., Coderre, E., Ridsdale, A., Zhang, L., Woulfe, J., Yin, X., Trapp, B.D., McRory, J.E., Rehak, R., Zamponi, G.W., Wang, W., Stys, P.K. Nature (2006) [Pubmed]
 
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