Drug transport to the brain:: Key roles for the efflux pump P-glycoprotein in the blood-brain barrier

被引：162

作者：

Demeule, M

Régina, A

Jodoin, J

Laplante, A

Dagenais, C

Berthelet, F

Moghrabi, A

Béliveau, R

机构：

[1] Univ Quebec, Hop St Justine, Mol Med Lab, Montreal, PQ H3C 3P8, Canada

[2] Hop Notre Dame de Bon Secours, Dept Pathol, Montreal, PQ H2L 4K8, Canada

[3] Hop St Justine, Unit Hemato Oncol, Montreal, PQ H3T 1C5, Canada

来源：

VASCULAR PHARMACOLOGY | 2002年 / 38卷 / 06期

关键词：

blood-brain barrier; P-glycoprotein; multidrug resistance; endothelial cells; caveolae;

D O I：

10.1016/S1537-1891(02)00201-X

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

1. The blood-brain barrier (BBB) contributes to brain homeostastis and fulfills a protective function by controlling the access of solutes and toxic substances to the central nervous system (CNS). The efflux transporter P-glycoprotein (P-gp) is a key element of the molecular machinery that confers special permeability properties to the BBB. 2. P-gp, which was initially recognized for its ability to expel anticancer drugs from multidrug-resistant cancer cells, is strongly expressed in brain capillaries. Its expression in the BBB limits the accumulation of many hydrophobic molecules and potentially toxic substances in the brain. 3. The purpose of this review is to summarize the current state of knowledge about the expression of P-gp, its cellular localization as well as its possible functions in the BBB. (C) 2002 Elsevier Science Inc. All rights reserved.

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收藏

页码：339 / 348

页数：10

相关论文

共 105 条

[11] A family of drug transporters: The multidrug resistance-associated proteins [J].

Borst, P ;

Evers, R ;

Kool, M ;

Wijnholds, J .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2000, 92 (16) :1295-1302

[12] ABC transporters in lipid transport [J].

Borst, P ;

Zelcer, N ;

van Helvoort, A .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2000, 1486 (01) :128-144

[13] Enforced P-glycoprotein pump function in murine bone marrow cells results in expansion of side population stem cells in vitro and repopulating cells in vivo [J].

Bunting, KD ;

Zhou, S ;

Lu, TH ;

Sorrentino, BP .

BLOOD, 2000, 96 (03) :902-909

[14] LOCALIZATION OF THE HUMAN MULTIPLE-DRUG RESISTANCE GENE, MDR1, TO 7Q21.1 [J].

CALLEN, DF ;

BAKER, E ;

SIMMERS, RN ;

SESHADRI, R ;

RONINSON, IB .

HUMAN GENETICS, 1987, 77 (02) :142-144

[15] Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects [J].

Cascorbi, I ;

Gerloff, T ;

Johne, A ;

Meisel, C ;

Hoffmeyer, S ;

Schwab, M ;

Schaeffeler, E ;

Eichelbaum, M ;

Brinkmann, U ;

Roots, I .

CLINICAL PHARMACOLOGY & THERAPEUTICS, 2001, 69 (03) :169-174

[16] STRUCTURE AND EXPRESSION OF THE HUMAN MDR (P-GLYCOPROTEIN) GENE FAMILY [J].

CHIN, JE ;

SOFFIR, R ;

NOONAN, KE ;

CHOI, K ;

RONINSON, IB .

MOLECULAR AND CELLULAR BIOLOGY, 1989, 9 (09) :3808-3820

[17] Screening of multidrug-resistance sensitive drugs by in situ brain perfusion in P-glycoprotein-deficient mice [J].

Cisternino, S ;

Rousselle, C ;

Dagenais, C ;

Scherrmann, JM .

PHARMACEUTICAL RESEARCH, 2001, 18 (02) :183-190

[18] OVEREXPRESSION OF A TRANSPORTER GENE IN A MULTIDRUG-RESISTANT HUMAN LUNG-CANCER CELL-LINE [J].

COLE, SPC ;

BHARDWAJ, G ;

GERLACH, JH ;

MACKIE, JE ;

GRANT, CE ;

ALMQUIST, KC ;

STEWART, AJ ;

KURZ, EU ;

DUNCAN, AMV ;

DEELEY, RG .

SCIENCE, 1992, 258 (5088) :1650-1654

[19] MULTIDRUG-RESISTANCE GENE (P-GLYCOPROTEIN) IS EXPRESSED BY ENDOTHELIAL-CELLS AT BLOOD-BRAIN BARRIER SITES [J].

CORDONCARDO, C ;

OBRIEN, JP ;

CASALS, D ;

RITTMANGRAUER, L ;

BIEDLER, JL ;

MELAMED, MR ;

BERTINO, JR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (02) :695-698

[20] EXPRESSION OF THE MULTIDRUG RESISTANCE GENE-PRODUCT (P-GLYCOPROTEIN) IN HUMAN NORMAL AND TUMOR-TISSUES [J].

CORDONCARDO, C ;

OBRIEN, JP ;

BOCCIA, J ;

CASALS, D ;

BERTINO, JR ;

MELAMED, MR .

JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 1990, 38 (09) :1277-1287

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