Abstract

The organic anion transporters 1 and 3 (OAT1 and OAT3), and organic cation transporter 2 (OCT2) are important for renal tubular drug secretion. In contrast, evidence for OAT2 expression in the human kidney is limited, and its role in renal drug transport is unknown. Both mRNA (real-time polymerase chain reaction) and protein (Western blotting) for OAT2 was detected in renal cortex from eight donors, and interindividual variability in protein levels was 3-fold. OAT2 protein in the renal cortex was localized (by immunohistochemistry) to the basolateral domain of tubules, as were OAT1 and OAT3. The absolute abundance of OAT2 mRNA was similar to OAT1 mRNA, 3-fold higher than OCT2 mRNA, but 10-fold lower than OAT3 mRNA. A previous observation that OAT2 transports cyclic guanosine monophosphate (cGMP) led us to examine if acyclovir, ganciclovir and penciclovir are OAT2 substrates; they are guanine-containing antivirals that undergo active tubular secretion. Transport of the antivirals into human embryonic kidney cells was stimulated 10- to 20-fold by expression of OAT2, but there was little to no transport of the antivirals by OAT1, OAT3 or OCT2. The K_m values for acyclovir, ganciclovir and penciclovir transport were 94 μM, 264 μM and 277 μM, respectively, and transport efficiencies were relatively high (6 to 24 µl•min^-1•mg protein^-1). This study provides definitive evidence for the expression of OAT2 in the human kidney, and is the first to demonstrate that OAT2, compared to OAT1, OAT3 or OCT2, has a preference for antiviral drugs mainly eliminated in the urine via active secretion.