Multidrug resistance protein I-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 (MRPI) in microglia, the primary brain cellular target of HIV In the present study, we further examine subcellular localization of MRPI in a microglia cell line (MLS-9) using immunogold cytochemistry and directly demonstrate MRPI-mediated export of saquinavir. MRPI localized primarily to the plasma membrane of the MLS-9 cells. [C-14]Saquinavir efflux by MLS-9 monolayers was inhibited by well-established MRPI inhibitors. These results indicate that MRPI contributes, in part, to the overall low permeation of protease inhibitors in the brain.