PT  - JOURNAL ARTICLE
AU  - Bhagwat Prasad
AU  - Katherine Johnson
AU  - Sarah Billington
AU  - Caroline Lee
AU  - Git W. Chung
AU  - Colin D.A. Brown
AU  - Edward J. Kelly
AU  - Jonathan Himmelfarb
AU  - Jashvant D. Unadkat
TI  - Abundance of Drug Transporters in the Human Kidney Cortex as Quantified by Quantitative Targeted Proteomics
AID  - 10.1124/dmd.116.072066
DP  - 2016 Dec 01
TA  - Drug Metabolism and Disposition
PG  - 1920--1924
VI  - 44
IP  - 12
4099  - http://dmd.aspetjournals.org/content/44/12/1920.short
4100  - http://dmd.aspetjournals.org/content/44/12/1920.full
SO  - Drug Metab Dispos2016 Dec 01; 44
AB  - Protein expression of renal uptake and efflux transporters was quantified by quantitative targeted proteomics using the surrogate peptide approach. Renal uptake transporters assessed in this study included organic anion transporters (OAT1–OAT4), organic cation transporter 2 (OCT2), organic/carnitine cation transporters (OCTN1 and OCTN2), and sodium-glucose transporter 2 (SGLT2); efflux transporters included P-glycoprotein, breast cancer resistance protein, multidrug resistance proteins (MRP2 and MRP4), and multidrug and toxin extrusion proteins (MATE1 and MATE2-K). Total membrane was isolated from the cortex of human kidneys (N = 41). The isolated membranes were digested by trypsin and the digest was subjected to liquid chromatography–tandem mass spectrometry analysis. The mean expression of surrogate peptides was as follows (given with the standard deviation, in picomoles per milligram of total membrane protein): OAT1 (5.3 ± 1.9), OAT2 (0.9 ± 0.3), OAT3 (3.5 ± 1.6), OAT4 (0.5 ± 0.2), OCT2 (7.4 ± 2.8), OCTN1 (1.3 ± 0.6), OCTN2 (0.6 ± 0.2), P-glycoprotein (2.1 ± 0.8), MRP2 (1.4 ± 0.6), MRP4 (0.9 ± 0.6), MATE1 (5.1 ± 2.3), and SGLT2 (3.7 ± 1.8). Breast cancer resistance protein (BCRP) and MATE2-K proteins were detectable but were below the lower limit of quantification. Interestingly, the protein expression of OAT1 and OAT3 was significantly correlated (r > 0.8). A significant correlation was also observed between expression of multiple other drug transporters, such as OATs/OCT2 or OCTN1/OCTN2, and SGLT2/OCTNs, OCT, OATs, and MRP2. These renal transporter data should be useful in deriving in vitro to in vivo scaling factors to accurately predict renal clearance and kidney epithelial cell exposure to drugs or their metabolites.