Induction of intestinal multidrug resistance-associated protein 2 (Mrp2) by spironolactone in rats.
Eur J Pharmacol
; 623(1-3): 103-6, 2009 Nov 25.
Article
em En
| MEDLINE
| ID: mdl-19766108
ABSTRACT
The effect of spironolactone (SL) pretreatment (200micromol/kg b.w./day, 3 consecutive days) on intestinal multidrug resistance-associated protein 2 (Mrp2) was evaluated in rats. A significant increase in protein levels in upper regions of small intestine, where Mrp2 is mainly present, was detected by western blotting. Real time PCR studies suggest a transcriptional regulation. The administration of ketoconazole, a pregnane X receptor (PXR) antagonist, was able to prevent the increase in Mrp2 mRNA levels induced by SL. The serosal to mucosal transport of dinitrophenyl S-glutathione, a model substrate of Mrp2 was evaluated in jejunal sac model. The data indicate that SL increased Mrp2 activity, well correlating with its up-regulation. We conclude that SL is able to induce intestinal Mrp2 transcriptionally, PXR being a potential mediator. We propose that SL could be of potential therapeutic application particularly in situations of down-regulation of intestinal Mrp2.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Espironolactona
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Regulação da Expressão Gênica
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Proteínas Associadas à Resistência a Múltiplos Medicamentos
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Intestino Delgado
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article