Zinc has been shown to be present in synaptic vesicles of a subset of glutamatergic boutons and is believed to be core-leased with glutamate at these synapses. A variety of studies have suggested that zinc might play a role in modulation of excitatory transmission, as well as excitotoxicity, by inhibiting N-methyl-D-aspartate (NMDA)-type glutamate receptors. To further investigate the modulator...

A monoclonal antibody (R1JHL) against the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor has been developed that recognizes an epitope in the region of the amino-terminal amino acids 341-561 (a region common to all splice variants of NR1). This monoclonal antibody identifies a broad band at 115 kDa in immunoblots using membranes from NR1-transfected cells and from rat brain tissue. No ...

Canonical NMDA receptors assemble from two glycine-binding NR1 subunits with two glutamate-binding NR2 subunits to form glutamate-gated excitatory receptors that mediate synaptic transmission and plasticity. The role of glycine-binding NR3 subunits is less clear. Whereas in Xenopus laevis oocytes, two NR3 subunits coassemble with two NR1 subunits to form a glycine-gated receptor, such a recepto...

The NR3A subunit of the N-methyl-D-aspartate receptor has been shown to form glutamatergic receptor complexes with NR1 and NR2 subunits and excitatory glycinergic receptor complexes with NR1 alone. 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 th...

Cellular-specific splicing of the retinal NMDAR1 receptor (NR1) and expression of NMDAR2 receptor (NR2) subunits in response to optic nerve injury was investigated by in situ hybridization in adult rats. A controlled optic nerve crush led to a clear alteration in the expression of alternatively spliced NR1 variants in the retinal ganglion cell layer (GCL). The NR1-2b and NR1-4b isoforms were pr...

NR1/NR2A is a subtype of N-methyl-d-aspartate receptors (NMDARs), which are glutamate and glycine-gated Ca(2+)-permeable channels highly expressed in the central nervous system. A high-throughput screening (HTS) campaign using human osteosarcoma (U-2 OS) cells transiently transduced with NR1/NR2A NMDAR subunits, tested in a specifically designed fluorometric imaging plate reader (FLIPR)/Ca(2+) ...

Kinetically distinct contributions of NMDA receptor NR1 and NR2 subunits to channel gating have recently been inferred by Banke and Traynelis from single-channel recordings of recombinant NR1–NR2B receptors. The results suggest a new mechanism for receptor activation that will enhance our insight into excitatory synaptic transmission in the brain. In the post-genomic era, this represents an exc...

The supraoptic nucleus (SON) of the hypothalamus contains magnocellular neurosecretory neurons (MNC) which synthesize and release the peptide hormones vasopressin and oxytocin. Glutamate is a prominent excitatory neurotransmitter in the SON and regulates MNC excitability. NMDA receptors (NMDAR), a type of ionotropic glutamate receptor, mediate synaptic plasticity of MNCs and are necessary for c...

Subunits of the NMDA receptor (NMDAR) associate with many postsynaptic proteins that substantially broaden its signaling capacity. Although much work has been focused on the signaling of NR2 subunits, little is known about the role of the NR1 subunit. We set out to elucidate the role of the C terminus of the NR1 subunit in NMDAR signaling. By introducing a C-terminal deletion mutant of the NR1 ...

The steady-state mRNA levels of the NMDA receptor NR1 subunit were determined by a quantitative solution hybridization assay in selected CNS regions associated with antinociception in the rat. Tissues were obtained by microdissection from rats treated chronically with morphine alone or in combination with LY274614, a competitive NMDA receptor antagonist. Morphine treatment for 7 days resulted i...