Expression and function of multidrug resistance transporters at the blood-brain barriers.
The presence of active carrier-mediated transport of substrates from the brain to the blood is a major feature of the barrier properties of the blood-brain barrier (BBB). These proteins lie in the luminal or abluminal membranes of the endothelial cells that form the BBB. Some are ATP-binding cassette proteins (ABC) and many amphipathic cationic drugs are carried by P-glycoprotein (ABCB1) or ABCG2, which lie at the luminal pole of the BBB. Several multidrug resistance-associated proteins (MRPs, ABCCs) are also present on the membranes of brain microvessels; these are mainly involved in the efflux of anionic compounds. All these ABC proteins help to protect the brain and form a critical target for CNS pharmaceuticals, influencing the clinical variability of responses to, and the design of, these drugs.
Scherrmann
Jean-Michel
JM
INSERM U705, CNRS UMR7157, University Paris 7, University Paris 5, Hôpital Fernand Widal, 200 rue du Faubourg Saint-Denis, 75475 Paris cedex 10, France. jean-michel.scherrmann@fwidal.inserm.fr
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D027361:Organic Anion Transporters / Q000235:genetics* / Q000378:metabolism
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D027361:Organic Anion Transporters; C513055:ABCB1 protein, human; C116614:ABCG2 protein, human