Abstract
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.
Original language | English (US) |
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Pages (from-to) | 1183-1186 |
Number of pages | 4 |
Journal | NeuroReport |
Volume | 15 |
Issue number | 7 |
DOIs | |
State | Published - May 19 2004 |
Externally published | Yes |
Keywords
- Brain transport
- Human immunodeficiency virus
- Microglia
- Multidrug resistance protein 1
- Saquinavir
ASJC Scopus subject areas
- General Neuroscience