Induction of intestinal multidrug resistance-associated protein 2 (Mrp2) by spironolactone in rats
| Autor: | María Laura Ruiz, Marcelo G. Luquita, Juan Pablo Rigalli, Aldo D. Mottino, José M. Pellegrino, Enrique J. Sánchez Pozzi, Viviana A. Catania, Silvina Stella Maris Villanueva, Agostina Arias |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Receptors Steroid medicine.medical_specialty Spironolactone Biology Polymerase Chain Reaction chemistry.chemical_compound Internal medicine Intestine Small Dinitrochlorobenzene medicine Animals RNA Messenger Rats Wistar Receptor Pharmacology Pregnane X receptor Microvilli Multidrug resistance-associated protein 2 Pregnane X Receptor Antagonist Cell Polarity Biological Transport Glutathione Multidrug Resistance-Associated Protein 2 Small intestine Rats Blot Endocrinology medicine.anatomical_structure Gene Expression Regulation chemistry Organ Specificity Ketoconazole Dinitrophenyl Multidrug Resistance-Associated Proteins medicine.drug |
| Zdroj: | European Journal of Pharmacology. 623:103-106 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2009.09.014 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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