Altered plasma membrane ultrastructure in multidrug-resistant cells.
Multidrug resistance is mediated by P-glycoprotein, an integral plasma membrane component which is thought to function as a drug export pump. This model can explain drug resistance, but fails to account for the broader pleiotropy of the multidrug resistance phenotype. We report here a freeze-fracture study revealing increases in the densities of protoplasmic face intramembrane particles in multidrug-resistant Chinese hamster ovary (CHO) and human leukemic cells. The intramembrane particle density in a CHO cell revertant which had lost the characteristics of the multidrug resistance phenotype was indistinguishable from that of the drug-sensitive parental cell line. This demonstration of a global multidrug resistance-linked change in plasma membrane architecture may have significant implications for understanding the variety of concurrent membrane-related changes which are not easily explained by the current model for multidrug resistance.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000648:ultrastructure*; D004351:Drug Resistance; D005614:Freeze Fracturing; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis; D008854:Microscopy, Electron
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins