title: Expression of P-glycoprotein in human cerebral cortex microvessels.
abstract: P-Glycoprotein (P-gp) is an ATP-dependent efflux transporter that extrudes non-polar molecules, including cytotoxic substances and drugs, from the cells. It was initially found in cancer cells and then was shown to be a normal component of complex transport systems working at the blood-brain barrier (BBB). Previous studies have demonstrated that, in the brain, P-gp is localized on the luminal plasmalemma of BBB endothelial cells and that it may interact with the caveolar compartment of these cells. The aim of this study was to identify the site of cellular expression of P-gp in human brain in situ and to morphologically determine whether an association may exist between P-gp and caveolin-1, a structural and functional protein of the caveolar frame. The study was carried out on human cerebral cortex by immunoconfocal microscopy with antibodies to both P-gp and caveolin-1. The results show that P-gp marks the microvessels of the cortex and that the transporter is localized in the luminal endothelial compartment, where it co-localizes with caveolin-1. The demonstration of this co-localization of P-gp with caveolin-1 contributes a morphological backing to biochemical studies on P-gp/caveolin-1 relationships and leads us to suggest that interactions between these molecules may occur at the BBB endothelia.
authors.affiliation: Department of Human Anatomy and Histology, University of Bari School of Medicine, Italy. virgintino@histology.uniba.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Virgintino
authors.forename: David
authors.initials: D
authors.lastname: Robertson
authors.forename: Mariella
authors.initials: M
authors.lastname: Errede
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Benagiano
authors.forename: Francesco
authors.initials: F
authors.lastname: Girolamo
authors.forename: Eugenio
authors.initials: E
authors.lastname: Maiorano
authors.forename: Luisa
authors.initials: L
authors.lastname: Roncali
authors.forename: Mirella
authors.initials: M
authors.lastname: Bertossi
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000368:Aged; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051272:Glucose Transporter Type 1; D006801:Humans; D008297:Male; D008833:Microcirculation; D018613:Microscopy, Confocal; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D005904:Glial Fibrillary Acidic Protein; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human