کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2533940 | 1559071 | 2009 | 4 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Induction of intestinal multidrug resistance-associated protein 2 (Mrp2) by spironolactone in rats Induction of intestinal multidrug resistance-associated protein 2 (Mrp2) by spironolactone in rats](/preview/png/2533940.png)
The effect of spironolactone (SL) pretreatment (200 μmol/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.
Journal: European Journal of Pharmacology - Volume 623, Issues 1–3, 25 November 2009, Pages 103–106