[3H]1-methyl-4-phenyl-2,3-dihydropyridinium ion binding sites in mouse brain: pharmacological and biological characterization.
J Neurochem
; 54(6): 1905-10, 1990 Jun.
Article
em En
| MEDLINE
| ID: mdl-2338548
Because 1-methyl-4-phenyl-2,3-dihydropyridinium ion (MPP+) appears to damage the dopaminergic neuron and cause neuronal death, we characterized [3H]MPP+ binding sites in mouse brain membranes. Among several compounds tested, debrisoquin [3,4-dihydro-2(1H)-isoquinolinecarboxamidine] and some analogues were able to antagonize [3H]MPP+ binding. Debrisoquin is able to block adrenergic transmission and inhibit the activity of monoamine oxidase A (MAO-A). We found a certain correlation between the ability of these agents to displace [3H]MPP+ from its binding sites and their capacity to inhibit MAO-A activity. These data and the finding of a higher number of [3H]MPP+ binding sites in human placenta compared to mouse brain suggest that these sites may correspond to MAO-A enzymes. Recently it has been demonstrated in human brain that neurons in regions rich in catecholamines are positive for MAO-A. Accordingly, we suggest MAO-A as a possible accumulation site of MPP+ within the dopaminergic neuron. We also indicate the chemical structural requirement associated with the best binding of debrisoquin analogues with [3H]MPP+ sites. It would be reasonable to test the effects of debrisoquin-like drugs able to pass the blood-brain barrier on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos de Piridínio
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Encéfalo
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
1990
Tipo de documento:
Article