Multidrug resistance-associated proteins (Mrps) are
ATP-dependent transporters which transport a wide variety of anionic and cationic compounds. The purpose of this study was to determine the tissue distribution of Mrp5 and 6 in male and female Sprague-Dawley rats in various tissues, and to investigate whether the expression is altered by
cholestasis or administration of microsomal
enzyme inducers (MEIs). These MEIs activate six different transcriptionally-mediated pathways, and their effects on Mrp5 and Mrp6 expression were determined. The effects of bile-duct
ligation, a
cholestasis model, on Mrp5 and 6 expression in male rats were quantified. Mrp5 had marked expression in adrenal gland, and moderate expression in cerebral cortex, cerebellum, and stomach. The MEIs
polychlorinated biphenyl (
PCB)126,
phenobarbital, and
PCB99 slightly repressed Mrp5, but no single class of receptor agonists induced or repressed Mrp5. Bile-duct
ligation tended to increase Mrp5 expression, but was not statistically significant at a 3 day timepoint. Mrp6 expression was highest in intestine, liver, and kidney. Mrp6 was slightly repressed by
phenobarbital,
dexamethasone, and
isoniazid, but no one class of receptor agonists induced or repressed Mrp6, and expression was also unchanged bile-duct
ligation. In conclusion, Mrp5 in rats is most highly expressed in the adrenal gland, whereas Mrp6 is mainly expressed in excretory organs (liver, intestine, and kidney), suggesting markedly different functions. Hepatic
mRNA levels of Mrp5 or Mrp6 do not seem to be coordinately regulated along with Phase I
enzymes via receptor-mediated pathways, and are not part of the hepatoprotective upregulation of basolateral transporters that occurs during
cholestasis.