Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was designed to determine the effects of chronic neonatal exposure to the NMDA receptor antagonist phencyclidine (PCP) on [3H]MK-801 binding and on gene expression of NMDA receptor subunits in juvenile male rats. Rat pups were injected daily with PCP from day 5 to 15 and killed on day 21. [3H]MK-801 binding was measured by quantitative autoradiography. A sensitive RNase protection assay was employed to determine simultaneously the mRNA levels of NR1 subunit (comprising all different splice variants) and three NR2 subunits (NR2A-NR2C). The relative distribution profile of NMDA receptor subunits in the cerebral cortex was NR2B > NR1 > NR2A > NR2C and in the cerebellum NR2C = NR1 > NR2A = NR2B. Chronic PCP administration in postnatal rats produced significant reduction in both [3H]MK-801 binding and mRNA level of the NR2B subunit in the cerebral cortex. Expression of the other NMDA receptor subunits in the cerebral cortex did not change following the drug treatment. In the cerebellum, neither [3H]MK-801 binding nor any of the NMDA receptor subunit expression levels showed any alteration. 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.
 ...
PMID:Postnatal phencyclidine treatment differentially regulates N-methyl-D-aspartate receptor subunit mRNA expression in developing rat cerebral cortex. 887 5

Phencyclidine (PCP) is a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor subtype. It produces transient psychoses in normal individuals and exacerbates psychoses in schizophrenics. When administered to rodents, PCP elicits stereotypic behaviors including unrelenting head swaying, hyperlocomotion, and social withdrawal. In this study, we examined the relative distribution of the NMDA receptor subunits, as well as the subunits of its modulating receptor, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) in the forebrain, hippocampus, and cerebellum of rats chronically exposed to PCP. Rats were injected for 30 days with PCP (10 mg/kg) and age/sex-matched controls were injected for 30 days with saline vehicle. Brain NMDA and AMPA receptor subunit distribution patterns and protein levels were then analyzed by immunocytochemistry and Western blot analysis. Chronic PCP-treated animals showed significant alterations in glutamate receptor subunits, particularly for the NR1, NR2B, NR2C, and NR2D components of the NMDA receptor. AMPA receptor subunits demonstrated few significant changes in subunit availabilities. Western blot analysis largely confirmed the immunocytochemical findings. These 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. Our findings are consistent with the interpretation that a dysfunctional NMDA receptor complex may mediate abnormal glutamatergic neurotransmission and potentially contribute to the complex etiology of cognitive disorders.
 ...
PMID:Glutamate receptor subunits are altered in forebrain and cerebellum in rats chronically exposed to the NMDA receptor antagonist phencyclidine. 1513 42