Expression and function of multidrug resistance transporters at the blood–brain barriers

Abstract

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.

Keywords::

• ABC proteins
• blood–brain barrier
• blood–cerebrospinal fluid barrier
• breast cancer resistance protein
• multidrug resistance-associated protein
• P-glycoprotein