Multidrug resistance protein 1-mediated transport of saquinavir by microglia.

Regulation of CNS distribution of the human immunodeficiency virus (HIV) protease inhibitor saquinavir may involve ATP-dependent membrane-bound efflux transport proteins that are expressed in several brain cellular compartments. We recently characterized molecular and functional expression of one such transporter, multidrug resistance protein-1 (MRP1) in microglia, the primary brain cellular target of HIV. In the present study, we further examine subcellular localization of MRP1 in a microglia cell line (MLS-9) using immunogold cytochemistry and directly demonstrate MRP1-mediated export of saquinavir. MRP1 localized primarily to the plasma membrane of the MLS-9 cells. [14C]Saquinavir efflux by MLS-9 monolayers was inhibited by well-established MRP1 inhibitors. These results indicate that MRP1 contributes, in part, to the overall low permeation of protease inhibitors in the brain. Copyright 2004 Lippincott Williams and Wilkins