PMID- 16365282
OWN - NLM
STAT- MEDLINE
DCOM- 20060419
LR  - 20131121
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 69
IP  - 3
DP  - 2006 Mar
TI  - Loss of synaptic D1 dopamine/N-methyl-D-aspartate glutamate receptor complexes in 
      L-DOPA-induced dyskinesia in the rat.
PG  - 805-12
AB  - Glutamate-mediated mechanisms are related to the motor complications of L-DOPA 
      therapy in Parkinson's disease (PD). In striatal postsynaptic densities (PSD), 
      the dopamine D1 receptor (D1R) is part of an oligomeric complex with the 
      glutamate N-methyl-D-aspartate receptor (NMDAR), determining the strength of 
      corticostriatal transmission. We studied D1R/NMDAR complex alterations induced by 
      L-DOPA in the 6-hydroxydopamine-lesioned rat model of PD. L-DOPA-treated 
      hemiparkinsonian rats were determined to be dyskinetic or nondyskinetic based on 
      behavioral testing. D1R/NMDAR assemblies containing NR1-C2 and NR2B subunits were 
      decreased in the PSD of lesioned striatum. Short-term L-DOPA administration 
      improved akinesia and restored the synaptic abundance of D1R, NR1-C2 and NR2B. 
      Prolonged L-DOPA treatment also normalized synaptic D1R/NMDAR complexes in 
      nondyskinetic rats, but remarkably reduced them in the dyskinetic group without 
      changing their interaction. This decrease involved NR1-C2, NR1-C2', NR2A, and 
      NR2B subunits. The composition of residual synaptic D1R/NMDAR complexes in 
      dyskinetic rats may thus be different from that observed in lesioned rats, 
      suggesting that expression of different motor dysfunctions might be related to 
      the receptor profile at corticostriatal synapses. The levels of D1R/NMDAR 
      complexes were unchanged in total striatal membrane proteins, suggesting that the 
      decrease of these species in the PSD is likely to reflect an altered receptor 
      trafficking. In human embryonic kidney 293 cells expressing the D1R/NMDAR, 
      complex costimulation of both D1R and NMDAR, but not individual receptor 
      activation, promoted internalization, suggesting that development of dyskinesias 
      might be related to agonist-mediated down-regulation of the D1R/NMDAR complex at 
      corticostriatal synapses.
FAU - Fiorentini, Chiara
AU  - Fiorentini C
AD  - Division of Pharmacology, Department of Biomedical Sciences and Biotechnology, 
      University of Brescia, Viale Europa 11, 25124 Brescia, Italy.
FAU - Rizzetti, Maria Cristina
AU  - Rizzetti MC
FAU - Busi, Chiara
AU  - Busi C
FAU - Bontempi, Sandra
AU  - Bontempi S
FAU - Collo, Ginetta
AU  - Collo G
FAU - Spano, PierFranco
AU  - Spano P
FAU - Missale, Cristina
AU  - Missale C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051219
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Antiparkinson Agents)
RN  - 0 (Protein Subunits)
RN  - 0 (Receptors, Dopamine D1)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 46627O600J (Levodopa)
RN  - 8HW4YBZ748 (Oxidopamine)
SB  - IM
MH  - Animals
MH  - Antiparkinson Agents/*toxicity
MH  - Cells, Cultured
MH  - Corpus Striatum/chemistry/metabolism
MH  - Dyskinesia, Drug-Induced/*metabolism
MH  - Humans
MH  - Levodopa/*toxicity
MH  - Male
MH  - Oxidopamine
MH  - Parkinson Disease, Secondary/chemically induced/*complications
MH  - Protein Subunits/analysis/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Dopamine D1/analysis/genetics/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/analysis/*metabolism
MH  - Synapses/chemistry/*metabolism
MH  - Transfection
EDAT- 2005/12/21 09:00
MHDA- 2006/04/20 09:00
CRDT- 2005/12/21 09:00
PHST- 2005/12/21 09:00 [pubmed]
PHST- 2006/04/20 09:00 [medline]
PHST- 2005/12/21 09:00 [entrez]
AID - mol.105.016667 [pii]
AID - 10.1124/mol.105.016667 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2006 Mar;69(3):805-12. doi: 10.1124/mol.105.016667. Epub 2005 Dec 
      19.