title: Multidrug resistance protein 1-mediated transport of saquinavir by microglia.
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.
authors.affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 19 Russell Street, Toronto, Ontario M5S 2S2, Canada.
authors.forename: Shannon
authors.initials: S
authors.lastname: Dallas
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Ronaldson
authors.forename: Moise
authors.initials: M
authors.lastname: Bendayan
authors.forename: Reina
authors.initials: R
authors.lastname: Bendayan
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology*; D002460:Cell Line; D017628:Microglia / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D051381:Rats; D019258:Saquinavir / Q000378:metabolism*
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; D019258:Saquinavir; C421109:multidrug resistance-associated protein 1