P-Glycoprotein in Clinical Cardiology

ver since Juliano and Ling first described P-glycoprotein (P-gp) in 1975, 1 it has become an important focus of research.P-gp is a member of the ATP-binding cassette (ABC) superfamily of proteins that is highly conserved in distantly related species (from simple eukaryotes to vertebrates). 2 These similarities across species suggest that P-gp plays an important role in physiological processes in normal cells.One established function is its active transport of drugs out of the cell against a concentration gradient using ATP as an energy source, which is unusual because unlike most energy-dependent pumps, it has very little substrate specificity.Humans have 2 known P-gp encoding genes, MDR1 (class I) and MDR2 (class III), both localized in chromosome 7. 3 The first has been associated with the phenomenon of multiple drug resistance (MDR), 4 and the second serves to transport phospholipids into the bile.5 Cloning and sequencing of the MDR gene led to the identification of the composition and structure of P-gp, 6 which consists of 2 membrane-bound domains (each with 6 transmembrane segments) and 2 nucleotide-binding domains that bind and hydrolyze ATP.