Roct1, a rat polyspecific transporter gene for the excretion of cationic drugs, maps to chromosome 1q11-12

Species: Rat. Locus name: Organic cation transporter, drug excretion. Locus symbol: Roct1. Map position: 1q11-12. Method of mapping: Fluorescence in situ hybridization (FISH). Database deposit information: GenBank/EMBL accession number X 78855. Molecular reagents: Plasmid pROCT1 was isolated from a rat kidney cDNA library by functional expression cloning in Xenopus oocytes and contains a 1882-bp cDNA insert. The whole plasmid was labeled by nick translation substituting biotin-16-dUTP for dTTP. FISH was performed as described elsewhere with 200 ng of probe DNA. Rat metaphase spreads were prepared from concanavalin A-stimulated blood lymphocyte cultures and fixed by standard acetic acid/methanol procedure. The hybridized probe was detected by FITC-conjugated avidin followed by one round of signal amplification with a biotinylated anti-avidin antibody. Chromosomes were counterstained with propidium iodide (PI) and 4'-6-diamidino-2-phenylindole (DAPI), and hybridization signals were visualized on a Zeiss Axiophot microscope equipped for epifluorescence. Discussion: In mammals, cationic drugs of different type and structure (for example, sedatives, antibiotics, cytostatics, opiates) are excreted through the epithelium of renal proximal tubules and liver hepatocytes. The recently discovered rat OCT1 protein is involved in this drug excretion. To differentiate the locus symbol of rat organic cation transporter from the former locus symbol for mouse octamer binding transcription factor (Oct1; now Otf1), we propose the locus symbol Roct1. Roct1 encodes a 556-amino acid membrane protein found in kidney, liver, and intestine. It mediates electrogenic transport of several endogenous organic cations and cationic drugs with different molecular structures. Besides the MDR family of multidrug transporting proteins, Roct1 is considered to be a second prototype of polyspecific drug transporters since it shares no homology, at the protein or DNA level, with any other known protein.