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 (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.
journal_name
Neuroreportjournal_title
Neuroreportauthors
Dallas S,Ronaldson PT,Bendayan M,Bendayan Rdoi
10.1097/00001756-200405190-00020subject
Has Abstractpub_date
2004-05-19 00:00:00pages
1183-6issue
7eissn
0959-4965issn
1473-558Xpii
00001756-200405190-00020journal_volume
15pub_type
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