Mechanism of Active Secretion of Phenolsulfonphthalein in the Liver via Mrp2 (abcc2), an Organic Anion Transporter

Abstract

Phenolsulfonphthalein (PSP) has been selected as a model drug that is eliminated from both the kidney and liver in rats. Although the renal PSP transport system has been studied, few details of the biliary excretion of PSP have been reported. We investigated the biliary excretion system for PSP in rats. It has been reported that the biliary excretion of many organic anions from hepatocytes into bile is mediated by a primary active transporter, referred to as multidrug resistance-associated protein 2 (Mrp2/abcc2). The biliary excretion of PSP in SD rats was significantly decreased in the presence of Mrp2 inhibitors. The biliary excretion of PSP in Eisai hyperbilirubinemic rats (EHBR), hereditarily Mrp2-defective rats, was significantly lower than that in SD rats. Moreover, an efflux experiment using Caco-2 cells was carried out to confirm Mrp2-mediated PSP transport. Mrp2 inhibitors significantly decreased PSP efflux from Caco-2 cells. These results suggest that Mrp2 contributes to the biliary excretion of PSP in SD rats.