Drug transport to the brain: key roles for the efflux pump P-glycoprotein in the blood-brain barrier.
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.
Demeule
Michel
M
Laboratoire de Médecine Moléculaire, Hôpital Sainte-Justine-Université du Québec à Montréal, C.P. 8888, Succursale Centre-ville, Montréal, Quebec, Canada H3C 3P8.
Régina
Anthony
A
Jodoin
Julie
J
Laplante
Alain
A
Dagenais
Claude
C
Berthelet
France
F
Moghrabi
Albert
A
Béliveau
Richard
R
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D001692:Biological Transport; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008833:Microcirculation / Q000166:cytology / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents