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.

journal_name

Neuroreport

journal_title

Neuroreport

authors

Dallas S,Ronaldson PT,Bendayan M,Bendayan R

doi

10.1097/00001756-200405190-00020

subject

Has Abstract

pub_date

2004-05-19 00:00:00

pages

1183-6

issue

7

eissn

0959-4965

issn

1473-558X

pii

00001756-200405190-00020

journal_volume

15

pub_type

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