Cloning and characterization of a potential-sensitive organic cation transporter (OCT3) from rat placenta

We have cloned a cDNA from a rat placental cDNA library which, when expressed in mammalian cells, mediates the transport of the organic cations tetraethylammonium, methylphenylpyridinium and guanidine. The cDNA-mediated transport, when studied in intact cells, is influenced by extracellular pH, the transport activity being higher at alkaline pH compared to acidic pH. Several other organic cations including N-methylnicotinamide, dimethylamiloride, nicotine, cimetidine, clonidine, and methylphenyltetrahydropyridine are also substrates for this transporter. The cloned transporter can also be expressed functionally in X. laevis oocytes by injection of cRNA. When studied under voltage-clamp conditions, the transporter activity is associated with inward currents, indicative of transfer of positive charge into the oocyte. The influence of external pH is negligible under these voltage-clamp conditions. The cDNA is 3,502 bp long and contains an open reading frame coding for a protein of 551 amino acids. This transporter is distinct from the recently cloned potential-sensitive organic cation transporters OCT1 and OCT2 and is also distinct from the kidney-specific NKT, a putative organic cation transporter. Northern blot analysis indicates that the transporter-specific mRNA is abundantly expressed in the placenta and moderately expressed in the brain, kidney, heart, lung, and intestine. The expression is not detectable in the liver.