Document Detail


Efflux mechanisms at the developing brain barriers: ABC-transporters in the fetal and postnatal rat.
MedLine Citation:
PMID:  20466047     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Proteins of the ATP-binding cassette (ABC) family, present at the blood-brain barrier interfaces, have been shown to reduce the entry of compounds from blood into the brain by active efflux. Their substrates are diverse including many drugs and toxins and therefore provide an important mechanism for brain neuroprotection. However, knowledge of their presence and function in the developing brain is very limited. We have used qPCR and immunocytochemistry to determine gene expression and localisation of four main barrier ABC-transporters (pgp/ABCB1, MRP1/ABCC1, MRP4/ABCC4 and BCRP/ABCG2) in the fetal and neonatal rat brain cerebral blood vessels (site of blood-brain barrier) and choroid plexus (site of blood-CSF barrier). The study shows that ABC-transporters localise to the brain barriers even at early fetal stages and although pgp expression was lower in the fetus, the other transporters were expressed at comparable levels in fetal and adult brains suggesting direct neuroprotection of the brain in addition to that provided by the placenta. BCRP was expressed at higher levels in developing choroid plexus and was only detected at fetal stages on the blood-facing side of epithelial cells indicating a particular role of this transporter for early brain efflux mechanisms.
Authors:
C Joakim Ek; Annamae Wong; Shane A Liddelow; Pia A Johansson; Katarzyna M Dziegielewska; Norman R Saunders
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-11
Journal Detail:
Title:  Toxicology letters     Volume:  197     ISSN:  1879-3169     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-08     Completed Date:  2010-07-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  51-9     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Department of Pharmacology, University of Melbourne, Parkville, Australia. cjek@unimelb.edu.au
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / genetics,  metabolism*
Animals
Biological Transport, Active
Blood-Brain Barrier / cytology,  growth & development,  metabolism*
Fetus / metabolism*
Multidrug Resistance-Associated Proteins / metabolism
P-Glycoprotein / metabolism
RNA, Messenger / metabolism
Rats
Chemical
Reg. No./Substance:
0/ATP-Binding Cassette Transporters; 0/Multidrug Resistance-Associated Proteins; 0/P-Glycoprotein; 0/RNA, Messenger

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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