title: P-glycoprotein is strongly expressed in the luminal membranes of the endothelium of blood vessels in the brain.
abstract: Luminal membranes of the vascular endothelium were isolated from brain, heart and lungs by modification of their density. The presence of P-glycoprotein (P-gp) was detected by Western blotting in luminal membranes from the endothelium of the three tissues. Strong enrichment in brain capillary luminal membranes, compared with brain capillaries (17-fold) and whole membranes (400-500-fold), indicates that P-gp is mainly located on the luminal side of the brain endothelium. Western blotting was also performed with antibodies directed against GLUT1, glial fibrillary acidic protein, adaptin, IP3R-3, integrins alphav and collagen IV as controls to determine whether the preparations were contaminated by other membranes. Strong enrichment of GLUT1 in brain capillary luminal membranes (9.9-fold) showed that the preparation consisted mainly of endothelial cell plasma membranes. Poor enrichment of glial fibrillary acidic protein (1.4-fold) and adaptin (2.4-fold) and a decreased level of IP3R-3, integrins alphav and collagen IV excludes the possibility of major contamination by astrocytes or internal and anti-luminal membranes. High levels of P-gp in the luminal membranes of brain capillary endothelial cells suggests that it may play an important role in limiting the access of anti-cancer drugs to the brain.
authors.affiliation: Laboratoire d'Oncologie Moléculaire, Départment de Chimie-Biochimie, Université du Québec à Montréal, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Beaulieu
authors.forename: M
authors.initials: M
authors.lastname: Demeule
authors.forename: L
authors.initials: L
authors.lastname: Ghitescu
authors.forename: R
authors.initials: R
authors.lastname: Béliveau
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000737:chemistry; D000345:Affinity Labels; D000818:Animals; D001386:Azides / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D002196:Capillaries / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002540:Cerebral Cortex / Q000098:blood supply; D004730:Endothelium, Vascular / Q000737:chemistry / Q000378:metabolism*; D006031:Glycosylation; D007457:Iodine Radioisotopes; D008297:Male; D011224:Prazosin / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000345:Affinity Labels; D001386:Azides; D007457:Iodine Radioisotopes; C041552:azidoprazosin; D011224:Prazosin