The physiological function of drug-transporting P-glycoproteins.
The mammalian drug-transporting or mdr1-type P-glycoproteins can extrude a range of structurally diverse, toxic xenobiotic compounds from cells. Our analysis of knockout mice lacking one or both of the mdr1-type P-glycoproteins indicates that a major function of these proteins is the protection of organisms against many of the toxic xenobiotics to which they can potentially be exposed in nature. P-glycoprotein confers protection by limiting the uptake of compounds from the gastrointestinal tract, and by stimulating excretion of compounds in the liver, kidney, and intestine. Moreover, P-glycoprotein in the blood-brain barrier and other blood-tissue barriers protects sensitive organs from exposure to toxic compounds that may have entered the bloodstream. Although we cannot exclude additional physiological functions for mdr1-type P-glycoproteins, these are not vital, since the mdr1-deficient mice are viable and fertile, and do not display obvious phenotypic abnormalities other than hypersensitivity to drugs.
Schinkel
A H
AH
Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D001812:Blood-Brain Barrier; D018432:Drug Resistance, Multiple; D006801:Humans; D051379:Mice; D010599:Pharmacokinetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1