MDR1 P-Glycoprotein Is a Lipid Translocase of Broad Specificity, While MDR3 P-Glycoprotein Specifically Translocates Phosphatidylcholine

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 phosphatidylcholine secretion into bile. After stable transfection of epithelial LLC-PK1 cells, MDR1 and MDR3 Pgp were localized in the apical membrane. At 15 degrees C, newly synthesized short-chain analogs of various membrane lipids were recovered in the apical a...

Multidrug Resistance Protein (P-Glycoprotein; MDR1)

In Situ Biochemical Demonstration That P-Glycoprotein Is a Drug Efflux Pump with Broad Specificity

While P-glycoprotein (Pgp) is the most studied protein involved in resistance to anti-cancer drugs, its mechanism of action is still under debate. Studies of Pgp have used cell lines selected with chemotherapeutics which may have developed many mechanisms of resistance. To eliminate the confounding effects of drug selection on understanding the action of Pgp, we studied cells transiently transf...

In vivo RNA interference-mediated ablation of MDR1 P-glycoprotein.

Multidrug resistance (MDR) remains a major obstacle to successful chemotherapeutic treatment of cancer and can be caused by overexpression of P-glycoprotein, the MDR1 gene product. To further validate a knockdown approach for circumventing MDR, we developed a P-glycoprotein inhibition strategy using short hairpin RNA interference (shRNAi) and now show efficacy and target specificity in vivo. Tw...

Determining P-glycoprotein-drug interactions: evaluation of reconstituted P-glycoprotein in a liposomal system and LLC-MDR1 polarized cell monolayers.

INTRODUCTION P-Glycoprotein (ABCB1, MDR1) is a multidrug efflux pump that is a member of the ATP-binding cassette (ABC) superfamily. Many drugs in common clinical use are either substrates or inhibitors of this transporter. Quantitative details of P-glycoprotein inhibition by pharmaceutical agents are essential for assessment of their pharmacokinetic behavior and prevention of negative patient ...