IFISE   05411
INSTITUTO DE FISIOLOGIA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Induction of intestinal multidrug resistance-associated protein 2 (Mrp2) by spironolactone in rats
Autor/es:
RUIZ ML; VILLANUEVA SSM; LUQUITA MG; PELLEGRINO JM; RIGALLI JP; ARIAS A; SÁNCHEZ POZZI EJ; MOTTINO AD; CATANIA VA
Revista:
EUROPEAN JOURNAL OF PHARMACOLOGY
Referencias:
Año: 2009 vol. 623 p. 103 - 106
ISSN:
0014-2999
Resumen:
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.