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 - PubMed (original) (raw)
Affiliations
- PMID: 10648644
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
A W Dunah et al. Mol Pharmacol. 2000 Feb.
Abstract
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.
Similar articles
- Loss of synaptic D1 dopamine/N-methyl-D-aspartate glutamate receptor complexes in L-DOPA-induced dyskinesia in the rat.
Fiorentini C, Rizzetti MC, Busi C, Bontempi S, Collo G, Spano P, Missale C. Fiorentini C, et al. Mol Pharmacol. 2006 Mar;69(3):805-12. doi: 10.1124/mol.105.016667. Epub 2005 Dec 19. Mol Pharmacol. 2006. PMID: 16365282 - Alterations of striatal NMDA receptor subunits associated with the development of dyskinesia in the MPTP-lesioned primate model of Parkinson's disease.
Hallett PJ, Dunah AW, Ravenscroft P, Zhou S, Bezard E, Crossman AR, Brotchie JM, Standaert DG. Hallett PJ, et al. Neuropharmacology. 2005 Mar;48(4):503-16. doi: 10.1016/j.neuropharm.2004.11.008. Neuropharmacology. 2005. PMID: 15755478 - Dopamine D1-dependent trafficking of striatal N-methyl-D-aspartate glutamate receptors requires Fyn protein tyrosine kinase but not DARPP-32.
Dunah AW, Sirianni AC, Fienberg AA, Bastia E, Schwarzschild MA, Standaert DG. Dunah AW, et al. Mol Pharmacol. 2004 Jan;65(1):121-9. doi: 10.1124/mol.65.1.121. Mol Pharmacol. 2004. PMID: 14722243 - Striatal mechanisms and pathogenesis of parkinsonian signs and motor complications.
Chase TN, Oh JD. Chase TN, et al. Ann Neurol. 2000 Apr;47(4 Suppl 1):S122-9; discussion S129-30. Ann Neurol. 2000. PMID: 10762139 Review. - Rationale for and use of NMDA receptor antagonists in Parkinson's disease.
Hallett PJ, Standaert DG. Hallett PJ, et al. Pharmacol Ther. 2004 May;102(2):155-74. doi: 10.1016/j.pharmthera.2004.04.001. Pharmacol Ther. 2004. PMID: 15163596 Review.
Cited by
- Targeting Striatal Glutamate and Phosphodiesterases to Control L-DOPA-Induced Dyskinesia.
Kochoian BA, Bure C, Papa SM. Kochoian BA, et al. Cells. 2023 Nov 30;12(23):2754. doi: 10.3390/cells12232754. Cells. 2023. PMID: 38067182 Free PMC article. Review. - NMDA receptor remodeling and nNOS activation in mice after unilateral striatal injury with 6-OHDA.
de Carvalho MB, Teixeira-Silva B, Marques SA, Silva AA, Cossenza M, da Cunha Faria-Melibeu A, Serfaty CA, Campello-Costa P. de Carvalho MB, et al. Heliyon. 2024 Jul 4;10(14):e34120. doi: 10.1016/j.heliyon.2024.e34120. eCollection 2024 Jul 30. Heliyon. 2024. PMID: 39130441 Free PMC article. - Potential future neuroprotective therapies for neurodegenerative disorders and stroke.
Tarawneh R, Galvin JE. Tarawneh R, et al. Clin Geriatr Med. 2010 Feb;26(1):125-47. doi: 10.1016/j.cger.2009.12.003. Clin Geriatr Med. 2010. PMID: 20176298 Free PMC article. Review. - cAMP response element-binding protein is required for dopamine-dependent gene expression in the intact but not the dopamine-denervated striatum.
Andersson M, Konradi C, Cenci MA. Andersson M, et al. J Neurosci. 2001 Dec 15;21(24):9930-43. doi: 10.1523/JNEUROSCI.21-24-09930.2001. J Neurosci. 2001. PMID: 11739600 Free PMC article. - Persistent behavioral sensitization to chronic L-DOPA requires A2A adenosine receptors.
Fredduzzi S, Moratalla R, Monopoli A, Cuellar B, Xu K, Ongini E, Impagnatiello F, Schwarzschild MA, Chen JF. Fredduzzi S, et al. J Neurosci. 2002 Feb 1;22(3):1054-62. doi: 10.1523/JNEUROSCI.22-03-01054.2002. J Neurosci. 2002. PMID: 11826134 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases