Localisation of breast cancer resistance protein in microvessel endothelium of human brain.
Movement of substrates between blood and brain is known to be influenced by P-glycoprotein (P-gp) at the luminal surface of the endothelium lining brain microvessels and by multidrug resistance associated protein 1 (MRP1) at the basolateral surface of the choroid plexus epithelium. Here, using RT-PCR and Western blotting, we investigate other ABC transporters in both normal and tumour human brain tissue and demonstrate the presence of breast cancer resistance protein (BCRP). Immunofluorescence confocal microscopy demonstrates that BCRP is located at the blood-brain barrier, mainly at the luminal surface of microvessel endothelium. This localization closely resembles that of P-gp. BCRP has several substrates in common with P-gp and may pose an additional barrier to drug access to the brain.
Cooray
Hiran C
HC
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK. hcc27@cam.ac.uk
Blackmore
Colin G
CG
Maskell
Lynn
L
Barrand
Margery A
MA
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000032:analysis*; D001812:Blood-Brain Barrier; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply*; D001932:Brain Neoplasms / Q000737:chemistry*; D004730:Endothelium, Vascular / Q000737:chemistry*; D005455:Fluorescent Antibody Technique; D051272:Glucose Transporter Type 1; D006801:Humans; D008833:Microcirculation; D018613:Microscopy, Confocal; D009004:Monosaccharide Transport Proteins / Q000032:analysis; D009363:Neoplasm Proteins / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
C116614:ABCG2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D009363:Neoplasm Proteins; C495677:SLC2A1 protein, human