Nigral and striatal regulation of angiotensin receptor expression by dopamine and angiotensin in rodents: implications for progression of Parkinson's disease.
Eur J Neurosci
; 32(10): 1695-706, 2010 Nov.
Article
em En
| MEDLINE
| ID: mdl-20964730
ABSTRACT
The basal ganglia have a local renin-angiotensin system and it has been shown that the loss of dopaminergic neurons induced by neurotoxins is amplified by local angiotensin II (AII) via angiotensin type 1 receptors (AT1) and nicotinamide adenine dinucleotide phosphate (NADPH) complex activation. Recent studies have revealed a high degree of counter-regulatory interactions between dopamine and AII receptors in non-neural cells such as renal proximal tubule cells. However, it is not known if this occurs in the basal ganglia. In the striatum and nigra, depletion of dopamine with reserpine induced a significant increase in the expression of AT1, angiotensin type 2 receptors (AT2) and the NADPH subunit p47(phox) , which decreased as dopamine function was restored. Similarly, 6-hydroxydopamine-induced chronic dopaminergic denervation induced a significant increase in expression of AT1, AT2 and p47(phox) , which decreased with L-dopa administration. A significant reduction in expression of AT1 mRNA was also observed after administration of dopamine to cultures of microglial cells. Transgenic rats with very low levels of brain AII showed increased AT1, decreased p47 (phox) and no changes in AT2 expression, whereas mice deficient in AT1 exhibited a decrease in the expression of p47 (phox) and AT2. The administration of relatively high doses of AII (100 nm) decreased the expression of AT1, and the increased expression of AT2 and p47(phox) in primary mesencephalic cultures. The results reveal an important interaction between the dopaminergic and local renin-angiotensin system in the basal ganglia, which may be a major factor in the progression of Parkinson's disease.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
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Angiotensina II
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Substância Negra
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Dopamina
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Corpo Estriado
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Receptor Tipo 1 de Angiotensina
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Receptor Tipo 2 de Angiotensina
Limite:
Animals
Idioma:
En
Revista:
Eur J Neurosci
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Espanha