MDR1 P-GLYCOPROTEIN IS A LIPID TRANSLOCASE OF BROAD-SPECIFICITY, WHILE MDR3 P-GLYCOPROTEIN SPECIFICALLY TRANSLOCATES PHOSPHATIDYLCHOLINE

The human MDR1 P-glycoprotein (Pgp) extrudes a variety of drugs across the plasma membrane. The homologous MDR3 Pgp is required for phosphat idylcholine secretion into bile. After stable transfection of epitheli al LLC-PK1 cells, MDR1 and MDR3 Pgp were localized in the apical membr ane. At 15 degrees C, newly synthesized short-chain analogs of various membrane lipids were recovered in the apical albumin-containing mediu m of MDR1 cells but not control cells. MDR inhibitors and energy deple tion reduced apical release. MDR3 cells exclusively released a short-c hain phosphatidylcholine. Since no vesicular secretion occurs at 15 de grees C, the short-chain lipids must have been translocated by the Pgp s across the plasma membrane before extraction into the medium by the lipid-acceptor albumin.