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. [14C]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.
- Brain transport
- Human immunodeficiency virus
- Multidrug resistance protein 1
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