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Titolo:
BIOTRANSFORMATION OF L-DOPA TO DOPAMINE IN THE SUBSTANTIA-NIGRA OF FREELY MOVING RATS - EFFECT OF DOPAMINE-RECEPTOR AGONISTS AND ANTAGONISTS
Autore:
SARRE S; VANDENEEDE D; EBINGER G; MICHOTTE Y;
Indirizzi:
FREE UNIV BRUSSELS,INST PHARMACEUT,DEPT PHARMACEUT CHEM & DRUG ANAL,LAARBEEKLAAN 103 B-1090 BRUSSELS BELGIUM FREE UNIV BRUSSELS,INST PHARMACEUT,DEPT PHARMACEUT CHEM & DRUG ANAL B-1090 BRUSSELS BELGIUM UNIV HOSP,DEPT NEUROL BRUSSELS BELGIUM
Titolo Testata:
Journal of neurochemistry
fascicolo: 4, volume: 70, anno: 1998,
pagine: 1730 - 1739
SICI:
0022-3042(1998)70:4<1730:BOLTDI>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMINO-ACID DECARBOXYLASE; BASAL GANGLIA; STRIATAL DOPAMINE; MOVEMENT-DISORDERS; PARKINSONS-DISEASE; CONSCIOUS RATS; D2 RECEPTORS; AWAKE RATS; IN-VIVO; RELEASE;
Keywords:
DOPAMINE; L-DOPA; MICRODIALYSIS; SUBSTANTIA NIGRA; DOPAMINE RECEPTOR AGONIST; DOPAMINE RECEPTOR ANTAGONIST;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
46
Recensione:
Indirizzi per estratti:
Citazione:
S. Sarre et al., "BIOTRANSFORMATION OF L-DOPA TO DOPAMINE IN THE SUBSTANTIA-NIGRA OF FREELY MOVING RATS - EFFECT OF DOPAMINE-RECEPTOR AGONISTS AND ANTAGONISTS", Journal of neurochemistry, 70(4), 1998, pp. 1730-1739

Abstract

We investigated the effects of continuous intranigral perfusion of dopamine D1 and D2 receptor agonists and antagonists on the biotransformation of locally applied L-DOPA to dopamine in the substantia nigra offreely moving rats by means of in vivo microdialysis. The ''dual-probe'' mode was used to monitor simultaneously changes in extracellular dopamine levels in the substantia nigra and the ipsilateral striatum, Intranigual perfusion of 10 mu M L-DOPA for 20 min induced a significant 180-fold increase in extracellular nigral dopamine level. No effect of the intranigral L-DOPA administration was observed on dopamine levels in the ipsilateral striatum, suggesting a tight control of extracellular dopamine in the striatum after enhanced nigral dopamine levels, Continuous nigral infusion with the D1 receptor agonist CY 208243 (10 mu M) and with the D2 receptor agonist quinpirole at 10 mu M (a nonselective concentration) attenuated the L-DOPA-induced increase in dopamine in the substantia nigra by 85 and 75%, respectively. However, perfusion of the substantia nigra with a lower concentration of quinpirole (1 mu M) and the D1 antagonist SCH 23390 (10 mu M) did not affect the nigral L-DOPA biotransformation. The D2 antagonist (-)-sulpiride (10 mu M) also attenuated the L-DOPA-induced dopamine release in the substantia nigra to similar to 10% of that of the control experiments. We confirm that there is an important biotransformation of L-DOPA to dopamine in the substantia nigra. The high concentrations of dopamine formedafter L-DOPA administration may be the cause of dyskinesias or further oxidative stress in Parkinson's disease, Simultaneous administrationof D1 receptor agonists with L-DOPA attenuates the biotransformation of L-DOPA to dopamine in the substantia nigra. The observed effects could occur via changes in nigral GABA release that in turn influence the firing rate of the nigral dopaminergic neurons.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 18:09:07