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Titolo:
Effect of dopamine denervation and dopamine agonist administration on serine phosphorylation of striatal nmda receptor subunits
Autore:
Oh, JD; Vaughan, CL; Chase, TN;
Indirizzi:
NINCDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA NINCDS Bethesda MD USA 20892 herapeut Branch, NIH, Bethesda, MD 20892 USA
Titolo Testata:
BRAIN RESEARCH
fascicolo: 2, volume: 821, anno: 1999,
pagine: 433 - 442
SICI:
0006-8993(19990313)821:2<433:EODDAD>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
D-ASPARTATE RECEPTOR; DEPENDENT PROTEIN-KINASE; MOTOR RESPONSE ALTERATIONS; LONG-TERM POTENTIATION; PARKINSONS-DISEASE; TYROSINE PHOSPHORYLATION; BASAL GANGLIA; GLUTAMATE ANTAGONIST; POSTSYNAPTIC DENSITY; RAT STRIATUM;
Keywords:
Parkinson's disease; 6-hydroxydopamine lesion; basal ganglia; NMDA antagonist; KN93; motor response alterations;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
72
Recensione:
Indirizzi per estratti:
Indirizzo: Chase, TN NINCDS,,Expt Therapeut Branch, NIH, Bldg 10,Room 5C103,90900 Rockville Pike NINCDS Bldg 10,Room 5C103,90900 Rockville Pike Bethesda MD USA 20892
Citazione:
J.D. Oh et al., "Effect of dopamine denervation and dopamine agonist administration on serine phosphorylation of striatal nmda receptor subunits", BRAIN RES, 821(2), 1999, pp. 433-442

Abstract

Sensitization of striatal N-methyl-D-aspartate (NMDA) receptors has been implicated in the pathogenesis of the response alterations associated with dopaminomimetic treatment of parkinsonian animals and patients. To determinewhether serine phosphorylation of NMDA receptor subunits by activation of Ca2+/calmodulin-dependent protein-kinase Il (CaMKII) contributes to this process, we examined the effects of unilateral nigrostriatal ablation with B-hydroxydopamine and subsequent treatment with levodopa, SKF 38393 (D1-preferring dopamine agonist), or quinpirole (D2-preferring agonist) on motor responses and phosphorylation states. Three weeks of twice-daily levodopa administration to rats shortened the duration of their rotational response to levodopa or SKF 38393 challenge, but prolonged the duration of quinpirole-induced rotation. At the same time, levodopa treatment elevated serine phosphorylation of striatal NR2A (p < 0.02), but not that of NR2B subunits, without associated changes in subunit protein levels. Chronic treatment with SKF38393 increased NR2A (p < 0.0001) but decreased NR2B (p < 0.004) serine phosphorylation. In contrast, chronic quinpirole treatment had no effect on NR2A but increased NR2B phosphorylation (p < 0.0001). The acute intrastriatal injection of the CaMKII inhibitor KN93 (1.0 mu g) not only normalized thelevodopa-induced motor response alterations but also attenuated the D1 andD2 receptor-mediated serine phosphorylation of NR2A and NR2B subunits, respectively (p < 0.02). These results suggest that a CaMKII-mediated rise in serine phosphorylation of NMDA receptor subunits induced by intermittent stimulation of D1 or D2 dopaminergic receptors contributes to the apparent enhancement in striatal NMDA receptor sensitivity and thus to the dopaminergic response plasticity in levodopa-treated parkinsonian rats. (C) 1999 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 08:51:11