Genetic dissection of the function of mammalian P-glycoproteins.
Mammalian P-glycoproteins are plasma membrane proteins belonging to the superfamily of ATP-binding cassette transporters. They were discovered as drug pumps in multidrug-resistant cancer cells, but are also present in many normal tissues. Genetic approaches have helped to dissect the physiological functions and mode of action of P-glycoproteins. Disruption of both genes for the drug-transporting P-glycoproteins in mice has no effect on the normal sheltered life of these mice, but renders them hypersensitive to many drugs. P-glycoprotein appears to be especially important in protecting the brain and in limiting uptake of hydrophobic drugs from the gut. Recent experiments with polarized cells support the idea that drug-transporting P-glycoproteins act by flipping drugs from the inner to the outer leaflet of the plasma membrane.
Borst
P
P
The Netherlands Cancer Institute, Department of Molecular Biology, Amsterdam, The Netherlands.
Schinkel
A H
AH
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000145:classification / Q000502:physiology*; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D018118:Chloride Channels / Q000378:metabolism; D004351:Drug Resistance / Q000502:physiology*; D008322:Mammals / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D004364:Pharmaceutical Preparations / Q000378:metabolism; D013379:Substrate Specificity
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018118:Chloride Channels; D004364:Pharmaceutical Preparations