Pglycoprotein

Pglycoprotein, commonly referred to as P-glycoprotein (P-gp) or ABCB1/MDR1, is an ATP-binding cassette (ABC) transporter that functions as an energy-dependent efflux pump located in the plasma membrane. It transports a wide range of hydrophobic compounds out of cells, using energy from ATP hydrolysis to drive substrate extrusion. In humans, P-glycoprotein is expressed at key barrier and excretory sites, including the apical membranes of intestinal epithelial cells, hepatocytes, renal proximal tubule cells, and the endothelium of the blood–brain barrier, as well as in placenta and other tissues.

Structurally, P-glycoprotein consists of two homologous halves, each with a transmembrane domain that forms the substrate-binding pocket and a nucleotide-binding domain that binds and hydrolyzes ATP. The transport cycle couples substrate binding with ATP binding and hydrolysis, producing conformational changes that move substrates from the cytoplasmic side toward the extracellular space or luminal membranes.

Physiologically, P-glycoprotein shapes drug pharmacokinetics by limiting intestinal absorption, promoting biliary and renal excretion, and restricting brain penetration. It plays a notable role in chemotherapy resistance, as tumor cells can overexpress P-glycoprotein to eject anticancer drugs.

Clinically and clinically relevant research areas focus on genetic variability (ABCB1 polymorphisms) and drug–drug interactions that modulate expression or activity. Inhibitors or inducers can significantly alter drug exposure and CNS penetration, informing considerations in drug development and personalized medicine.