Disease relevance of Grin2c

• In vitro hypoxia induces expression of the NR2C subunit of the NMDA receptor in rat cortex and hippocampus [1].
• MSG treatment (4 mg/g body weight, on postnatal days 1, 3, 5, and 7) produced an important increase of NR2C and NR2D subunit gene expression levels in the hippocampus and striatum of adults rats [2].

Psychiatry related information on Grin2c

• 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 [3].

High impact information on Grin2c

• The properties of these 'low-conductance' channels correspond to those described for recombinant NMDA receptors formed by coexpression of NR1 and NR2C subunits [4].
• The apparent affinity for Zn2+ of the heteromeric NMDA receptors is determined by the subtype of NR2 subunit expressed, with NR2A-containing receptors being the most sensitive (IC50, approximately 20 nM) and NR2C-containing receptors being the least sensitive (IC50, approximately 30 microM) [5].
• However, the predicted slowing of decay kinetics to a value more characteristic of NR2C deactivation, was not seen until P40 [6].
• In culture, 25 mM KCl or NMDA rapidly induced NR2A and downregulated NR2B, followed by gradual induction of NR2C [7].
• An en passant observation concerned high levels of NR2C mRNA in the pineal gland [8].

Chemical compound and disease context of Grin2c

• In addition, increases in tyrosine phosphorylation of the NR2A/B subunits, but not of the NR2C subunit, of the N-methyl-D-aspartate receptor occurred at 5, 30, and 60 min of hypoxia in the dorsocaudal brain stem and returned to baseline values at 120 min [9].

Biological context of Grin2c

• In situ granule-cell maturation is associated with downregulation of NR2B and increases both of NR2A and NR2C and in the ratio of NR1b/NR1a mRNAs [7].
• Neuronal plasticity reorganizations in the vestibular nuclei following unilateral labyrinthectomy appear to include only changes in NR1 and NR2C mRNA levels modifying the functional diversity of the NMDA receptor in the ipsilateral medial vestibular nucleus neurons [3].
• Duality of glutamatergic and GABAergic control of pulsatile GnRH secretion by rat hypothalamic explants: II. Reduced NR2C- and GABAA-receptor-mediated inhibition at initiation of sexual maturation [10].
• A 400 bp NR2C promoter region upstream of the transcriptional start site was identified as a basal promoter that was negatively regulated possibly by a neuron restrictive silencer element (NRSE) that is localized 664 base pairs downstream from the transcriptional start sites [11].
• We have used the L-2-chloropropionic acid (L-CPA) (750 mg/kg) model of NMDA-mediated selective cerebellar granule cell necrosis in vivo to examine the role of the glycine binding site and possible effect of the NR2C subunit (which is largely expressed only in the cerebellum) on granule cell necrosis [12].

Anatomical context of Grin2c

• NMDAR2A and NMDAR2C expressed individually in Xenopus oocytes showed no electrophysiological response to agonists [13].
• This pattern was identical to that observed for cerebellar (NR2C-containing) versus forebrain (NR2A- and NR2B-containing) NMDA receptors [14].
• The signals for NR2C mRNA appeared in granule cells and glial cells during the second postnatal week [15].
• NR2C and NR2D subunit messenger RNAs was examined by in situ hybridization in neuroendocrine cells of the supraoptic nucleus one month after amygdala kindling to stage 5 seizures [16].
• NMDAR2C is present in the substantia nigra pars compacta only, while NMDAR2D exhibits an unusual distribution, with high levels of expression in the substantia nigra pars compacta, the subthalamic nucleus, the globus pallidus, and the ventral pallidum [17].

Associations of Grin2c with chemical compounds

• The use of quinolinic acid and homoquinolinic acid may thus help to identify endogenous receptors containing the NR2C subunit [18].
• Thus, the high expression of NR2C in vasopressin cells relative to oxytocin cells may make these cells more susceptible to glutamatergic activation [19].
• Analogues of 16b bearing aroyl or aryl substituents attached to the N(1) position of piperazine-2,3-dicarboxylic acid have been synthesized to probe the structural requirements for NR2C/NR2D selectivity [20].
• Thus, the NR2B subunit "permits" both forms of spermine potentiation, the NR2A subunit permits spermine potentiation only by increasing the glycine affinity, and th NR2C subunit permits neither form of potentiation [21].
• NR2C subunit mRNA expression was unaltered in short-term gentamicin rats [22].

Regulatory relationships of Grin2c

• We therefore suggest that the glycine site plays a lesser role in modulating NMDA receptor function in the cerebellum and may explain why cells expressing NMDA receptors composed of NR1/NR2C subunits are particularly resistant to excitatory amino acid-induced neurotoxicity [12].

Other interactions of Grin2c

• Vasopressin cells exhibited 5-fold higher NR2C (32%), approximately half as much NR2B mRNA (39%) and equivalent NR2D (31%) [19].
• NR2C staining was confined to cerebellum, thalamus and olfactory bulb [23].
• Reversal of glutamate excitotoxicity by activation of PKC-associated metabotropic glutamate receptors in cerebellar granule cells relies on NR2C subunit expression [24].
• No mGluR5, NMDAR2A and NMDAR2C immunoreactivity was detected [25].
• We found that depletion of the NR2C subunit abolished the inhibitory effect of group I mGluR stimulation on glutamate-induced [Ca2+]i rise and neurotoxicity [24].

Analytical, diagnostic and therapeutic context of Grin2c

• RT-PCR studies performed on tissue preparations of adult rats also revealed a distinct expression of NR2C mRNA [26].
• The NMDAR2C subunit was detected in PC12 cells by Northern blotting and trace amounts of NMDAR2A, B and D were detected by PCR [27].
• Western blot analysis revealed that NR1 (P= 0.009) and NR2C (P= 0.003) protein abundance was significantly higher in the renal cortex short-term gentamicin rats [22].
• Eight weeks after transplantation, analysis demonstrated acquisition of an adult differentiation status reflected by abundant GABAA alpha 6 and NR2C mRNA expression in granule cells [28].

References