UM
Increased expression of neuronal Src and tyrosine phosphorylation of NMDA receptors in rat brain after systemic treatment with MK-801
Linden A.-M.1; Storvik M.1; Lakso M.1; Haapasalo A.1; Lee D.1; Witkin J.M.2; Sei Y.3; Castren E.1; Wong G.1
2001-03-24
Source PublicationNeuropharmacology
ISSN00283908
Volume40Issue:4Pages:469-481
AbstractWe have observed that systemic treatment with the uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 increases Src expression and NMDA receptor phosphorylation in rat brain. A partial cDNA encoding rat neuronal Src was isolated and its sequence was used to design specific oligonucleotide probes. Systemically administered MK-801 (5 mg/kg for 4 h) increased by 28±4% mRNA expression of neuronal Src in the superficial layers of the parietal cortex. This effect was observed at doses as low as 0.2 mg/kg. A similar, although more modest, induction was observed 6 h after phencyclidine (15 mg/kg) administration, but not after high doses of memantine and ketamine. The MK-801-induced effect was not blocked by pretreatment with clozapine. Consistent with the increase in mRNA levels, cortical Src protein was increased to 186 ± 24% of control 24 h after MK-801 treatment. Total cellular Src activity was also increased in parietal cortex homogenates 4 h after MK-801 (5 mg/kg). Moreover, MK-801 treatment (0.5 mg/kg and 5 mg/kg for 4 h) increased tyrosine phosphorylation, but not protein levels, of the NMDA receptor subunit NR2A. These results provide evidence for a contribution of Src and tyrosine phosphorylation of NMDA receptors in the pharmacological actions of uncompetitive NMDA receptor antagonists. © 2001 Elsevier Science Ltd.
KeywordCerebral cortex Cloning Dizocilpine Phencyclidine Tyrosine kinase
DOI10.1016/S0028-3908(00)00185-4
URLView the original
Language英語
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Cited Times [WOS]:8   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Itä-Suomen yliopisto
2.NIDA Addiction Research Center
3.Uniformed Services University of the Health Sciences
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Linden A.-M.,Storvik M.,Lakso M.,et al. Increased expression of neuronal Src and tyrosine phosphorylation of NMDA receptors in rat brain after systemic treatment with MK-801[J]. Neuropharmacology,2001,40(4):469-481.
APA Linden A.-M..,Storvik M..,Lakso M..,Haapasalo A..,Lee D..,...&Wong G..(2001).Increased expression of neuronal Src and tyrosine phosphorylation of NMDA receptors in rat brain after systemic treatment with MK-801.Neuropharmacology,40(4),469-481.
MLA Linden A.-M.,et al."Increased expression of neuronal Src and tyrosine phosphorylation of NMDA receptors in rat brain after systemic treatment with MK-801".Neuropharmacology 40.4(2001):469-481.
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