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.
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