DRUG EXCRETION MEDIATED BY A NEW PROTOTYPE OF POLYSPECIFIC TRANSPORTER

CATIONIC drugs of different types and structures (antihistaminics, ant iarrhythmics, sedatives, opiates, cytostatics and antibiotics, for exa mple) are excreted in mammals by epithelial cells of the renal proxima l tubules and by hepatocytes in the liver(1-4). In the proximal tubule s, two functionally disparate transport systems are involved which are localized in the basolateral and luminal plasma membrane and are diff erent from the previously identified neuronal monoamine transporters a nd ATP-dependent multidrug exporting proteins(1-3,5-12). Here we repor t the isolation of a complementary DNA from rat kidney that encodes a 556-amino-acid membrane protein, OCT1, which has the functional charac teristics of organic cation uptake over the basolateral membrane of re nal proximal tubules and of organic cation uptake into hepatocytes. OC T1 is not homologous to any other known protein and is found in kidney , liver and intestine. As OCT1 translocates hydrophobic and hydrophili c organic cations of different structures, it is considered to be a ne w prototype of polyspecific transporters that are important for drug e limination.