TY - JOUR T1 - Interspecies Variability in Expression of Hepatobiliary Transporters across Human, Dog, Monkey and Rat as Determined by Quantitative Proteomics JF - Drug Metabolism and Disposition JO - Drug Metab Dispos DO - 10.1124/dmd.114.061580 SP - dmd.114.061580 AU - Li Wang AU - Bhagwat Prasad AU - Laurent Salphati AU - Xiaoyan Chu AU - Anshul Gupta AU - Cornelis E.C.A. Hop AU - Raymond Evers AU - Jash D Unadkat Y1 - 2014/12/22 UR - http://dmd.aspetjournals.org/content/early/2014/12/22/dmd.114.061580.abstract N2 - We quantified, by LC-MS/MS, transporter protein expression of BSEP, MATE1, MRP3, MRP4, NTCP, and OCT1 in our human liver bank (n=55) and determined the relationship between protein expression and sex, age and genotype. These data complement our previous work in the same liver bank where we quantified the protein expression of OATPs, BCRP, MDR1, and MRP2. In addition, we quantified and compared the interspecies differences in expression of the hepatobiliary transporters, corresponding to the above human transporters, in liver tissue and hepatocytes of male beagle dogs, cynomolgus monkeys, Sprague-Dawley and Wistar rats. In all the species, the sinusoidal OATPs/Oatps were the most abundant hepatic transporters. However, there were notable interspecies differences in the relative abundance of the remaining transporters. For example, the next most abundant transporter in humans and monkeys was OCT1/Oct1 while it was Mrp2 and Ntcp in dogs/Wistar rats and Sprague-Dawley rats, respectively. In contrast, the protein expression of the efflux transporters, BCRP/Bcrp, MDR1/Mdr1, MRP3/Mrp3, MRP4/Mrp4, MATE1/Mate1 was much lower across all the species. For most transporters, the expression in the liver tissues was comparable to that in the unplated cryopreserved hepatocytes. These data on human liver transporter protein expression complete the picture of the expression of major human hepatobiliary transporters important in drug disposition and toxicity. In addition, the data on expression of the corresponding hepatobiliary transporters in preclinical species will be helpful in interpreting and extrapolating pharmacokinetic, pharmacological, and toxicological results from pre-clinical studies to humans. ER -