Cloning and Tissue-specific Expression of Spliced Variants of the Rat Organic Anion Transporter (rOAT-K)

Abstract

During the last decade, molecular cloning has identified several families of multispecific organic ion transporters mediating the renal and hepatic elimination of organic ions. Clinically, these transporters play important roles in the renal tubular secretion and reabsorption of various drugs. They are also in part responsible for the drug pharmacologic responses, drug-drug interactions, and drug nephrotoxicity. This study describes 12 novel isoforms of the rat kidney organic anion transporter rOAT-K. These isoforms are spliced variants of the same gene arising from alternative splicing of six regions defined as A-F. The two previously reported isoforms rOAT-K1 and rOAT-K2 were also found to be spliced variants of this gene. The open reading frames of the 12 isoforms encode a range of 352-670 amino acid proteins. Tissue distribution studies showed that the majority of the isoforms are kidney- and liver-specific.