A REEVALUATION OF SUBSTRATE-SPECIFICITY OF THE RAT CATION TRANSPORTERROCT1

The substrate specificity of the previously cloned rat cation transpor ter rOCT1, which is expressed in kidney, liver, and small intestine, w as reevaluated. rOCT1 is the first member of a new protein family comp rising electrogenic and polyspecific cation transporters that transpor t hydrophilic cations like tetraethylammonium, choline, and monoamine neurotransmitters. Previous electrical measurements suggested that cat ions like quinine, quinidine, and cyanine 863, which have been classif ied as type 2 cations in the liver, are also transported by rOCT1, sin ce they may induce inward currents in rOCT1 expressing Xenopus oocytes (Busch, A. E., Quester, S., Ulzheimer, J. C., Waldegger, S., Gorboule v, V., Arndt, P., Lang, F., and Koepsell, H. (1996) J. Biol. Chem. 271 , 32599-32604). Tracer flux measurements with oocytes and with stably transfected human embryonic kidney cells showed that [H-3]quinine and [H-3]quinidine are not transported by rOCT1. The voltage dependence ob served for the quinine-or quinidine-induced inward currents in rOCT1-e xpressing oocytes, and tracer efflux measurements indicate that the in ward currents by type 2 cations are generated by the inhibition of el ectrogenic efflux of transported type I cations. Therefore, rOCT1 cann ot contribute to transport of type 2 cations in the liver and the hepa tic transporter for type 2 cations remains to be identified.