Multidrug resistance protein Mrp2 mediates ATP-dependent transport of classic renal organic anion p-aminohippurate

p-Aminohippurate (PAH) is widely used as a model substrate to characterize organic anion transport in kidney proximal tubules. The carrier responsible for uptake of PAH across the basolateral membrane has been cloned and well characterized, whereas transporters mediating PAH excretion across the bru sh-border (apical) membrane are yet unknown. In this study we investigated whether PAH is a substrate for the apical multidrug resistance protein 2 (M rp2). Overexpression of recombinant rabbit Mrp2 in Sf9 cells significantly increased ATP-dependent [C-14]PAH uptake into isolated membrane vesicles co mpared with endogenous ATP-dependent uptake. The Michaelis-Menten constant and maximal velocity for Mrp2-mediated ATP-dependent [C-14]PAH transport we re 1.9 +/- 0.8 mM and 187 +/- 29 pmol.mg(-1).min(-1), respectively. On the basis of the inhibitory profile, the endogenous ATP-dependent PAH transport er does not appear to be an ortholog of Mrp2. Together, our results show th at Mrp2 is a low-affinity ATP-dependent PAH transporter, indicating that Mr p2 might contribute to urinary PAH excretion.