Efflux mechanism of organic anions mediated by active transport system in the intestinal membrane

摘要

P-Glycoprotein (Pgp), encoded by the mdr1 gene, has been implicated in the expulsion of many structurally and functionally unrelated rugs from tumor cells, canalicular membrane in the liver and brain microvessel endothelial cells. Recently, some investigators reported that the intestinal absorption of some compounds was limited partly because they are preferentially transported in the secretory di8rection by a Pgp transport system. On the other hand, it was recently reported that the multidrug resistance protein (MRP), which belongs to the ATP-binding cassette transporter superfamily of membrane transport protein like Pgp, transports calcein, an organic anion, from the cytoplasmic compartment of tumor cells and it stransport is ATP-dependent. We previously reported that calcein was excreted from the normal intestinal mucosal cel membrane by an MRP-like transprot system but not Pgp (1,2). In this report, we further studied the efflux mechanism of calcein and other probenecid, a classical substrate for organic anion transporter, mediated by the MRP-like protein from the intestinal membrane using a human intestinal adenocarcinoma cell line, Caco-2.