Regulation of the Rat Organic Anion-transporting Polypeptide 4 (oatp4) By Bile Acids

摘要

Hepatocellular uptake of organic anions including bile salts across the basolateral membrane is mediated by members of the organic anion-transporting polypeptide (Oatp) family of transporters1. In the rat five Oatp family members have been cloned (Oatpl-5) and have been shown to be expressed in a tissue-specific manner2. In rat liver, Oatpl (Slc21al), Oatp2 (Slc21a5) and Oatp4 (Slc21alO) are expressed at the basolateral membrane of hepatocytes3"5. While Oatpl is also expressed in kidney and Oatp2 is also expressed in brain, the recently cloned Oatp4 is exclusively expressed in liver5. Together with human OATP2 and 0ATP8, rat Oatp4 belongs to a subfamily of liver-specific Oatps and exhibits 64% and 66% amino acid identity with human 0ATP2 and 0ATP8, respectively6^8. Oatp4 substrates include cholyl taurine, bromosulphophthalein, dehydroepiandrosterone sulphate, leukotriene C4 and the anionic cyclopentapeptide BQ-123.