Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1

The rat organic cation transporter (rOCT)-2 was characterized by electrical and tracer flux measurements compared with rOCT1. By applying choline grad ients to voltage-clamped Xenopus oocytes expressing rOCT2, potential-depend ent currents could be induced in both directions. Tracer flux measurements with seven organic cations revealed similar Michaelis-Menten constant value s for both transporters, with the exception of guanidine. In parallel exper iments with rOCT2 and rOCT1, inhibition of tetraethylammonium transport by 12 cations, 2 weak bases, corticosterone, and the anions para-amminohippura te, a-ketoglutarate, and probenecid was characterized. The IC50 values of m any inhibitors were similar for both transporters, whereas others were sign ificantly different. Mepiperphenidol and O-methylisoprenaline showed an sim ilar to 70-fold lower and corticosterone a 38-fold higher affinity for rOCT 2. With the use of these inhibitors together with previous information on c ation transporters, experimental protocols are proposed to dissect out the individual contributions of rOCT2 and rOCT1 in intact proximal tubule prepa rations. Inhibition experiments at different pH levels strongly suggest tha t the weak base quinine passively permeates the plasma membrane at physiolo gical pH and inhibits rOCT2 from the intracellular side.