Pglycoproteïne

Pglycoprotéine, commonly referred to as P-glycoprotein (P-gp), is a membrane transport protein expressed in many tissues. It is encoded by the ABCB1 gene in humans and belongs to the ATP-binding cassette (ABC) transporter superfamily. P-gp functions as an energy-dependent efflux pump that uses ATP hydrolysis to move a diverse set of substrates out of cells, reducing intracellular accumulation.

Structurally, P-gp consists of two homologous halves, each with six transmembrane helices and a cytoplasmic nucleotide-binding domain. This arrangement enables conformational changes that transport substrates from the cytoplasm to the extracellular space or lumen.

P-gp is highly expressed on the apical surface of intestinal enterocytes, in hepatocytes and renal proximal tubule cells, and on brain capillary endothelium. Its physiological roles include limiting oral drug absorption, promoting biliary and renal excretion, and restricting drug entry into the central nervous system, contributing to tissue protection and pharmacokinetic control.

Clinical significance of P-gp includes its impact on drug pharmacokinetics and interactions. Inhibitors such as verapamil and ritonavir can increase the oral bioavailability and brain penetration of P-gp substrates, while inducers like rifampin and St. John’s wort can enhance efflux and reduce drug effectiveness. Genetic variation in ABCB1, including polymorphisms such as C3435T, has been studied for associations with expression and transport activity, though findings are variable.

In oncology, overexpression of P-gp in tumor cells is linked to multidrug resistance by actively pumping anticancer agents out of cells. P-gp remains a key consideration in drug development and pharmacokinetic modeling due to its broad substrate range and impact on drug disposition.