Uncompetitive Antagonists of the N‐Methyl‐D‐aspartate (NMDA) Receptors Alter the mRNA Expression of Proteins Associated with the NMDA Receptor Complex

@article{Linden2001UncompetitiveAO,
  title={Uncompetitive Antagonists of the N‐Methyl‐D‐aspartate (NMDA) Receptors Alter the mRNA Expression of Proteins Associated with the NMDA Receptor Complex},
  author={A. -M. Linden and Jussi V{\"a}is{\"a}nen and Markus Storvik and Merja Lakso and Esa R. Korpi and Garry Wong and Eero Castr{\'e}n},
  journal={Pharmacology \& Toxicology},
  year={2001},
  volume={88},
  pages={98-105}
}
N-methyl-D-aspartate (NMDA) receptor function appears to be under complex control during physiological and pharmacological states. We have investigated the effects of acute administration of uncompetitive NMDA receptor antagonists on mRNA levels of NMDA receptor subunits and on molecules known to cluster or phosphorylate the receptor utilizing in situ hybridization on rat brain sections. A high dose (5 mg/kg; 4 hr) of dizocilpine (MK-801) decreased mRNA levels of NMDA receptor subunits NR2C and… Expand
Subunit selective decrease of AMPA and metabotropic glutamate receptor mRNA expression in rat brain by systemic administration of the NMDA receptor blocker MK-801
TLDR
Results indicate that selected AMPA and mGluR subunit mRNAs respond at the RNA level to the blockade of NMDA receptors. Expand
The N-methyl-D-aspartate receptor subunit NR2B: localization, functional properties, regulation, and clinical implications.
TLDR
The NR2B subunit of the NMDA receptor has been implicated in modulating functions such as learning, memory processing, pain perception, and feeding behaviors, as well as being involved in a number of human disorders. Expand
Expression Profiling to Understand Actions of NMDA/Glutamate Receptor Antagonists in Rat Brain
TLDR
The emerging picture generated by using expression profiling approaches, identifies several of what likely will be many molecules that take part in the complex events that occur during BDNF signaling mediated by blockade of NMDA/glutamate receptors as potential stress related molecules in brain. Expand
Glutamate Receptor Subunits are Altered in Forebrain and Cerebellum in Rats Chronically Exposed to the NMDA Receptor Antagonist Phencyclidine
TLDR
Results support the conclusion that subunits of the NMDA receptor are selectively altered by chronic PCP antagonism, with minimal to no changes observed in AMPA receptor subunits. Expand
The development- and phencyclidine-regulated induction of synapse-associated protein-97 gene in the rat neocortex
TLDR
Findings suggest that SAP97 might be involved in the molecular basis of the development-dependent onset of the non-dopaminergic symptoms seen in schizophrenia and the schizophrenia-like psychosis induced by NMDA receptor blocking. Expand
Reduction of glutamatergic neurotransmission by prolonged exposure to dieldrin involves NMDA receptor internalization and metabotropic glutamate receptor 5 downregulation.
TLDR
It is confirmed that permanent blockade of the GABA(A) receptor by this persistent pesticide triggers adaptive neuronal changes consisting of a reduction of glutamatergic neurotransmission, which might explain the cognitive and learning deficits observed in animals after chronic treatment with dieldrin. Expand
Long-lasting changes in hippocampal synaptic plasticity and cognition in an animal model of NMDA receptor dysfunction in psychosis
TLDR
It is argued that synaptic plasticity may be a better assay for assessing novel schizophrenia therapeutics than behavioural evaluation, and raised the question as to whether targeting the NMDA receptors or its modulators could prove an effective strategy in treatment of psychosis and schizophrenia. Expand
MK-801 Upregulates NR2A Protein Levels and Induces Functional Recovery of the Ipsilateral Hemidiaphragm Following Acute C2 Hemisection in Adult Rats
TLDR
The findings strengthen the evidence that the NR2A subunit plays a substantial role in mediating recovery of the paralyzed hemidiaphragm following C2 spinal cord hemisection. Expand
NMDAR Hypofunction Animal Models of Schizophrenia
TLDR
Animal models of NMDAR hypofunction generated by pharmacological and genetic approaches are reviewed and how they relate to the pathophysiology of schizophrenia are discussed. Expand
Selective reduction of a PDZ protein, SAP‐97, in the prefrontal cortex of patients with chronic schizophrenia
TLDR
Findings suggest that a phenotypic loss of SAP97 is associated with the postsynaptic impairment in prefrontal excitatory circuits of schizophrenic patients. Expand
...
1
2
...

References

SHOWING 1-10 OF 63 REFERENCES
Heteromeric NMDA Receptors: Molecular and Functional Distinction of Subtypes
TLDR
Molecular cloning identified three complementary DNA species of rat brain, encoding NMDA receptor subunits NMDAR2A (NR2A), NR2B, and NR2C, which are 55 to 70% ientical in sequence, and these are structurally related, with less than 20% sequence identity, to other excitatory amino acid receptor sub Units. Expand
Postnatal phencyclidine treatment differentially regulates N-methyl-D-aspartate receptor subunit mRNA expression in developing rat cerebral cortex.
TLDR
Together, these data provide a molecular correlate for chronic postnatal PCP-induced down-regulation of [3H]MK-801 binding in rat cerebral cortex and suggest that the NR2B subunit plays an important role in developmental plasticity. Expand
Regulation of N-methyl-D-aspartate receptor function by constitutively active protein kinase C.
TLDR
Application of PKM to inside-out patches taken from cultured neurons increased the probability of channel opening without changing single-channel current amplitudes or channel open times, indicating the activation of protein kinase C is associated with potentiation of NMDA receptor function in hippocampal neurons largely through an increase in the probabilityof channel opening. Expand
Chronic administration of a glycine partial agonist alters the expression of N-methyl-D-aspartate receptor subunit mRNAs.
TLDR
To investigate the possibility that chronic administration of ACPC alters N-methyl-D-aspartate (NMDA) receptor composition, the levels of mRNAs encoding zeta and epsilon subunits were quantified and it is hypothesized that alterations in NMDA receptor subunit composition may explain the neuroprotective effects produced by chronic ACPC. Expand
Expression of NMDA receptor subunit mRNA after MK-801 treatment in neonatal rats.
TLDR
Results indicate that gene expression for NMDA receptor subunits in the developing brain is rapidly altered after antagonist exposure, and increased expression of excitatory amino acid receptor subunit mRNA may contribute to the enhanced vulnerability to excitotoxic injury that has been observed after MK-801 treatment. Expand
NMDA receptor subunits in the postsynaptic density of rat brain: expression and phosphorylation by endogenous protein kinases.
TLDR
It is reported that NR1 and NR2A-2C subunits are all enriched in the postsynaptic density (PSD), which plays critical roles in trophin-mediated synaptic plasticity and indicates that the PSD is a coherent functional unit containing protein kinases that potentially regulate NMDA receptor function via phosphorylation. Expand
Inhibition of N-methyl-D-aspartate receptors by haloperidol: developmental and pharmacological characterization in native and recombinant receptors.
TLDR
Haloperidol interacts with NMDA receptors at a site distinct from the polyamine or ifenprodil sites, and the prototypic sigma ligand ditolylguanidine shows no preference between NR 1 a/2A and NR 1a/2B receptors, which suggests that haloperidl exerts its effects on the NMDA receptor at a distinct site from the pharmacologically defined sigma receptor. Expand
Protein kinase C reduces Mg2+ block of NMDA-receptor channels as a mechanism of modulation
THE roles of N-methyl-D-aspartate (NMDA) receptors and protein kinase C (PKC) are critical in generating and maintaining a variety of sustained neuronal responses. In the nociceptive (pain-sensing)Expand
Identification of a Phosphorylation Site for Calcium/Calmodulindependent Protein Kinase II in the NR2B Subunit of the N-Methyl-D-aspartate Receptor*
TLDR
It is shown that serine 1303 in the full-length NR2B and/or the cognate site in NR2A is a major site of phosphorylation of the receptor both in the postsynaptic density fraction and in living hippocampal neurons. Expand
Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases
TLDR
Data suggest that PDZ domains can function as modules for protein-protein interactions and members of the PSD-95 family might serve to anchor NMDA receptors to the submembrane cytoskeleton and aid in the assembly of signal transduction complexes at postsynaptic sites. Expand
...
1
2
3
4
5
...