PMID- 10648644
OWN - NLM
STAT- MEDLINE
DCOM- 20000302
LR  - 20131121
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 57
IP  - 2
DP  - 2000 Feb
TI  - Alterations in subunit expression, composition, and phosphorylation of striatal
      N-methyl-D-aspartate glutamate receptors in a rat 6-hydroxydopamine model of
      Parkinson's disease.
PG  - 342-52
AB  - Recent evidence has linked striatal N-methyl-D-aspartate (NMDA) receptor function
      to the adverse effects of long-term dopaminergic treatment in Parkinson's
      disease. We have studied the abundance, composition, and phosphorylation of NMDA 
      receptor subunits (NRs) in the rat 6-hydroxydopamine lesion model of
      parkinsonism. In lesioned striatum, the abundance of NR1 and NR2B in striatal
      membranes was decreased to 68 +/- 3.2 and 62 +/- 4.4%, respectively, relative to 
      the unlesioned striata, whereas the abundance of NR2A was unchanged.
      Coimmunoprecipitation of NMDA receptors under nondenaturing conditions revealed
      that these changes reflected a selective depletion of receptors composed of
      NR1/NR2B, without alteration in receptors composed of NR1/NR2A. However, the
      abundance and composition of striatal NMDA receptors in extracts containing both 
      cytoplasmic and membrane proteins were not altered in lesioned rats, suggesting
      that the changes in the membrane fraction resulted from intracellular
      redistribution of receptors. The phosphorylation of NR1 protein at serine 890 and
      serine 896, but not at serine 897, and the tyrosine phosphorylation of NR2B but
      not NR2A were decreased in the membrane fraction of the lesioned striatum.
      Chronic treatment of lesioned rats with L-dopa normalized the alterations in the 
      abundance and subunit composition of the NMDA receptors in striatal membranes,
      and produced striking hyperphosphorylation, both of NR1 at serine residues, and
      NR2A and NR2B at tyrosine residues. These findings suggest that the adverse motor
      effects of chronic L-dopa therapy may result from alterations in regulatory
      phosphorylation sites on NMDA receptors.
FAU - Dunah, A W
AU  - Dunah AW
AD  - Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts,
      USA.
FAU - Wang, Y
AU  - Wang Y
FAU - Yasuda, R P
AU  - Yasuda RP
FAU - Kameyama, K
AU  - Kameyama K
FAU - Huganir, R L
AU  - Huganir RL
FAU - Wolfe, B B
AU  - Wolfe BB
FAU - Standaert, D G
AU  - Standaert DG
LA  - eng
GR  - NS2830/NS/NINDS NIH HHS/United States
GR  - NS31579/NS/NINDS NIH HHS/United States
GR  - NS34361/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Antiparkinson Agents)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 46627O600J (Levodopa)
RN  - 8HW4YBZ748 (Oxidopamine)
SB  - IM
MH  - Animals
MH  - Antiparkinson Agents/pharmacology
MH  - Cell Membrane/drug effects/metabolism
MH  - Corpus Striatum/drug effects/*metabolism
MH  - Disease Models, Animal
MH  - Levodopa/pharmacology
MH  - Male
MH  - Neurons/drug effects/*metabolism
MH  - Oxidopamine
MH  - Parkinson Disease, Secondary/chemically induced/*metabolism
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/drug effects/*metabolism
EDAT- 2000/01/29 09:00
MHDA- 2000/03/04 09:00
CRDT- 2000/01/29 09:00
PHST- 2000/01/29 09:00 [pubmed]
PHST- 2000/03/04 09:00 [medline]
PHST- 2000/01/29 09:00 [entrez]
PST - ppublish
SO  - Mol Pharmacol. 2000 Feb;57(2):342-52.