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The human brain endothelial cell line hCMEC/D3 as a human blood-brain barrier model for drug transport studies

Poller, B. and Gutmann, H. and Krähenbühl, S. and Weksler, B. and Romero, I. and Couraud, P. O. and Tuffin, G. and Drewe, J. and Huwyler, J.. (2008) The human brain endothelial cell line hCMEC/D3 as a human blood-brain barrier model for drug transport studies. Journal of Neurochemistry, Vol. 107, H. 5. pp. 1358-1368.

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Official URL: http://edoc.unibas.ch/dok/A6003524

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Abstract

The human brain endothelial capillary cell line hCMEC/D3 has been developed recently as a model for the human blood-brain barrier. In this study a further characterization of this model was performed with special emphasis on permeability properties and active drug transport. Para- or transcellular permeabilities (P(e)) of inulin (0.74 x 10(-3) cm/min), sucrose (1.60 x 10(-3) cm/min), lucifer yellow (1.33 x 10(-3) cm/min), morphine (5.36 x 10(-3) cm/min), propranolol (4.49 x 10(-3) cm/min) and midazolam (5.13 x 10(-3) cm/min) were measured. By addition of human serum the passive permeability of sucrose could be reduced significantly by up to 39%. Furthermore, the expression of a variety of drug transporters (ABCB1, ABCG2, ABCC1-5) as well as the human transferrin receptor was demonstrated on the mRNA level. ABCB1, ABCG2 and transferrin receptor proteins were detected and functional activity of ABCB1, ABCG2 and the ABCC family was quantified in efflux experiments. Furthermore, ABCB1-mediated bidirectional transport of rhodamine 123 was studied. The transport rate from the apical to the basolateral compartment was significantly lower than that in the inverse direction, indicating directed p-glycoprotein transport. The results of this study demonstrate the usefulness of the hCMEC/D3 cell line as an in vitro model to study drug transport at the level of the human blood-brain barrier.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Klinische Pharmakologie > Klinische Pharmakologie (Krähenbühl)
03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Gastroenterology (Beglinger)
UniBasel Contributors:Drewe, Jürgen and Krähenbühl, Stephan and Gutmann, Heike and Huwyler, Jörg
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Wiley-Blackwell
ISSN:0022-3042
e-ISSN:1471-4159
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:28 Nov 2017 09:23
Deposited On:25 Apr 2014 08:00

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