RT Journal Article SR Electronic T1 CHARACTERIZATION OF TRANSPORT PROTEIN EXPRESSION IN MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN (MRP) 2-DEFICIENT RATS JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 556 OP 562 DO 10.1124/dmd.105.005793 VO 34 IS 4 A1 Brendan M. Johnson A1 Peijin Zhang A1 John D. Schuetz A1 Kim L. R. Brouwer YR 2006 UL http://dmd.aspetjournals.org/content/34/4/556.abstract AB Multidrug resistance-associated protein (Mrp) 2-deficient transport-deficient (TR–) rats, together with their transport-competent Wistar counterparts (wild type), have been used to examine the contribution of Mrp2 to drug disposition. However, little is known about potential variation in expression of other transport proteins between TR– and wild-type rats or whether these differences are tissue-specific. Sections of liver, kidney, brain, duodenum, jejunum, ileum, and colon were obtained from male TR– and wild-type Wistar rats. Samples were homogenized in protease inhibitor cocktail and ultracentrifuged at 100,000g for 30 min to obtain membrane fractions. Mrp2, Mrp3, Mrp4, P-glycoprotein, sodium-dependent taurocholate cotransporting polypeptide, organic anion transporting polypeptides 1a1 and 1a4, bile salt export pump, breast cancer resistance protein, ileal bile acid transporter, UDP-glucuronosyl transferase (UGT1a), glyceraldehyde-3-phosphate dehydrogenase, and β-actin protein expression were determined by Western blot. Mrp3 was significantly up-regulated in the liver (∼6-fold) and kidney (∼3.5-fold) of TR– rats compared with wild-type controls. Likewise, the expression of UGT1a enzymes was increased in the liver and kidney of TR– rats by ∼3.5- and ∼5.5-fold, respectively. Interestingly, Mrp3 expression was down-regulated in the small intestine of TR– rats, but expression was similar to wild type in the colon. Mrp4 was expressed to varying extents along the intestine. Expression of some transport proteins and UGT1a enzymes differ significantly between TR– and wild-type rats. Therefore, altered drug disposition in TR– rats must be interpreted cautiously because up- or down-regulation of other transport proteins may play compensatory roles in the presence of Mrp2 deficiency. The American Society for Pharmacology and Experimental Therapeutics