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PPAR.ALPHA. Agonists Positively and Negatively Regulate the Expression of Several Nutrient/Drug Transporters in Mouse Small Intestine

2007; Pharmaceutical Society of Japan; Volume: 30; Issue: 11 Linguagem: Inglês

10.1248/bpb.30.2185

1347-5215

Toshitake Hirai, Yuka Fukui, Kiyoto Motojima,

Metabolism, Diabetes, and Cancer

A systematic analysis to examine the effects of peroxisome proliferator-activated receptor (PPAR)α agonists on the expression levels of all the nutrient/drug plasma-membrane transporters in the mouse small intestine was performed. Transporter mRNAs that were induced or repressed by two independent PPARα-specific agonists were identified by a genome-wide microarray method, and the changes were confirmed by real-time PCR using RNA isolated from the intestines and livers of wild-type and PPARα-null mice. Expression levels of seven nutrient/drug transporters (Abcd3, Octn2/Slc22a5, FATP2/Slc27a2, Slc22a21, Mct13/Slc16a13, Slc23a1 and Bcrp/Abcg2) in the intestine were up-regulated and the expression level of one (Mrp1/Abcc1) was down-regulated by PPARα; although the previously report that the H+/peptide co-transporter 1 (Pept1) is up-regulated by PPARα was not replicated in our study. We propose that the transport processes can be coordinately regulated with intracellular metabolism by nutrient nuclear receptors.