Expression of P-glycoprotein in human cerebral cortex microvessels.
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.
Virgintino
Daniela
D
Department of Human Anatomy and Histology, University of Bari School of Medicine, Italy. virgintino@histology.uniba.it
Robertson
David
D
Errede
Mariella
M
Benagiano
Vincenzo
V
Girolamo
Francesco
F
Maiorano
Eugenio
E
Roncali
Luisa
L
Bertossi
Mirella
M
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
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