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Effect of Adenosine A(2A) Receptor Antagonists and l-DOPA on Hydroxyl Radical, Glutamate and Dopamine in the Striatum of 6-OHDA-Treated Rats

A(2A) adenosine receptor antagonists have been proposed as a new therapy of PD. Since oxidative stress plays an important role in the pathogenesis of PD, we studied the effect of the selective A(2A) adenosine receptor antagonists 8-(-3-chlorostyryl)caffeine (CSC) and 4-(2-[7-amino-2-(2-furyl)[1,2,4]...

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Autores principales: Gołembiowska, Krystyna, Dziubina, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer-Verlag 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246585/
https://www.ncbi.nlm.nih.gov/pubmed/21830163
http://dx.doi.org/10.1007/s12640-011-9263-x
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author Gołembiowska, Krystyna
Dziubina, Anna
author_facet Gołembiowska, Krystyna
Dziubina, Anna
author_sort Gołembiowska, Krystyna
collection PubMed
description A(2A) adenosine receptor antagonists have been proposed as a new therapy of PD. Since oxidative stress plays an important role in the pathogenesis of PD, we studied the effect of the selective A(2A) adenosine receptor antagonists 8-(-3-chlorostyryl)caffeine (CSC) and 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385) on hydroxyl radical generation, and glutamate (GLU) and dopamine (DA) extracellular level using a microdialysis in the striatum of 6-OHDA-treated rats. CSC (1 mg/kg) and ZM 241385 (3 mg/kg) given repeatedly for 14 days decreased the production of hydroxyl radical and extracellular GLU level, both enhanced by prior 6-OHDA treatment in dialysates from the rat striatum. CSC and ZM 241385 did not affect DA and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) extracellular levels in the striatum of 6-OHDA-treated rats. l-DOPA (6 mg/kg) given twice daily for two weeks in the presence of benserazide (3 mg/kg) decreased striatal hydroxyl radical and glutamate extracellular level in 6-OHDA-treated rats. At the same time, l-DOPA slightly but significantly increased the extracellular levels of DOPAC and HVA. A combined repeated administration of l-DOPA and CSC or ZM 241385 did not change the effect of l-DOPA on hydroxyl radical production and glutamate extracellular level in spite of an enhancement of extracellular DA level by CSC and elevation of extracellular level of DOPAC and HVA by ZM 241385. The data suggest that the 6-OHDA-induced damage of nigrostriatal DA-terminals is related to oxidative stress and excessive release of glutamate. Administration of l-DOPA in combination with CSC or ZM 241385, by restoring striatal DA-glutamate balance, suppressed 6-OHDA-induced overproduction of hydroxyl radical.
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spelling pubmed-32465852011-12-29 Effect of Adenosine A(2A) Receptor Antagonists and l-DOPA on Hydroxyl Radical, Glutamate and Dopamine in the Striatum of 6-OHDA-Treated Rats Gołembiowska, Krystyna Dziubina, Anna Neurotox Res Article A(2A) adenosine receptor antagonists have been proposed as a new therapy of PD. Since oxidative stress plays an important role in the pathogenesis of PD, we studied the effect of the selective A(2A) adenosine receptor antagonists 8-(-3-chlorostyryl)caffeine (CSC) and 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385) on hydroxyl radical generation, and glutamate (GLU) and dopamine (DA) extracellular level using a microdialysis in the striatum of 6-OHDA-treated rats. CSC (1 mg/kg) and ZM 241385 (3 mg/kg) given repeatedly for 14 days decreased the production of hydroxyl radical and extracellular GLU level, both enhanced by prior 6-OHDA treatment in dialysates from the rat striatum. CSC and ZM 241385 did not affect DA and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) extracellular levels in the striatum of 6-OHDA-treated rats. l-DOPA (6 mg/kg) given twice daily for two weeks in the presence of benserazide (3 mg/kg) decreased striatal hydroxyl radical and glutamate extracellular level in 6-OHDA-treated rats. At the same time, l-DOPA slightly but significantly increased the extracellular levels of DOPAC and HVA. A combined repeated administration of l-DOPA and CSC or ZM 241385 did not change the effect of l-DOPA on hydroxyl radical production and glutamate extracellular level in spite of an enhancement of extracellular DA level by CSC and elevation of extracellular level of DOPAC and HVA by ZM 241385. The data suggest that the 6-OHDA-induced damage of nigrostriatal DA-terminals is related to oxidative stress and excessive release of glutamate. Administration of l-DOPA in combination with CSC or ZM 241385, by restoring striatal DA-glutamate balance, suppressed 6-OHDA-induced overproduction of hydroxyl radical. Springer-Verlag 2011-08-10 2012 /pmc/articles/PMC3246585/ /pubmed/21830163 http://dx.doi.org/10.1007/s12640-011-9263-x Text en © The Author(s) 2011 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Article
Gołembiowska, Krystyna
Dziubina, Anna
Effect of Adenosine A(2A) Receptor Antagonists and l-DOPA on Hydroxyl Radical, Glutamate and Dopamine in the Striatum of 6-OHDA-Treated Rats
title Effect of Adenosine A(2A) Receptor Antagonists and l-DOPA on Hydroxyl Radical, Glutamate and Dopamine in the Striatum of 6-OHDA-Treated Rats
title_full Effect of Adenosine A(2A) Receptor Antagonists and l-DOPA on Hydroxyl Radical, Glutamate and Dopamine in the Striatum of 6-OHDA-Treated Rats
title_fullStr Effect of Adenosine A(2A) Receptor Antagonists and l-DOPA on Hydroxyl Radical, Glutamate and Dopamine in the Striatum of 6-OHDA-Treated Rats
title_full_unstemmed Effect of Adenosine A(2A) Receptor Antagonists and l-DOPA on Hydroxyl Radical, Glutamate and Dopamine in the Striatum of 6-OHDA-Treated Rats
title_short Effect of Adenosine A(2A) Receptor Antagonists and l-DOPA on Hydroxyl Radical, Glutamate and Dopamine in the Striatum of 6-OHDA-Treated Rats
title_sort effect of adenosine a(2a) receptor antagonists and l-dopa on hydroxyl radical, glutamate and dopamine in the striatum of 6-ohda-treated rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246585/
https://www.ncbi.nlm.nih.gov/pubmed/21830163
http://dx.doi.org/10.1007/s12640-011-9263-x
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