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.