The Open UniversitySkip to content
 

Polarized P-glycoprotein expression by the immortalised human brain endothelial cell line, hCMEC/D3, restricts apical-to-basolateral permeability to rhodamine 123

Tai, Leon M.; Reddy, P. Sreekanth; Lopez-Ramirez, M. Alejandro; Davies, Heather A.; Male, A. David K.; Loughlin, A. Jane and Romero, Ignacio A. (2009). Polarized P-glycoprotein expression by the immortalised human brain endothelial cell line, hCMEC/D3, restricts apical-to-basolateral permeability to rhodamine 123. Brain Research, 1292 pp. 14–24.

Full text available as:
[img]
Preview
PDF (Accepted Manuscript) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Download (438Kb)
DOI (Digital Object Identifier) Link: http://dx.doi.org/10.1016/j.brainres.2009.07.039
Google Scholar: Look up in Google Scholar

Abstract

P-glycoprotein (P-gp) expression at the blood-brain barrier prevents unwanted blood-borne toxins and signalling molecules from entering the brain. Primary and immortalised human brain endothelial cells (BECs) represent two suitable options for studying P-gp function in vitro. The limited supply of primary human BECs and their instability over passage number makes this choice unattractive for medium/high throughput studies. The aim of this study was to further characterise the expression of P-gp by an immortalised human BEC line, hCMEC/D3, in order to evaluate their use as an in vitro human blood-brain barrier model. P-gp expression was stable over a high passage number (up to passage 38) and was polarised on the apical plasma membrane, consistent with human BECs in vivo. In addition, hCMEC/D3 cell P-gp expression was comparable, albeit slightly lower to that observed in primary isolated human BECs although P-gp function was similar in both cell lines. The P-gp inhibitors tariquidar and vinblastine prevented the efflux of rhodamine 123 (rh123) from hCMEC/D3 cells, indicative of functional P-gp expression. hCMEC/D3 cells also displayed polarised P-gp transport, since both tariquidar and vinblasine selectively increased the apical-to-basolateral permeability of hCMEC/D3 cells to rh123. The results presented here demonstrate that hCMEC/D3 cells are a suitable model to investigate substrate specificity of P-gp in BECs of human origin.

Item Type: Journal Article
Copyright Holders: 2009 Elsevier
ISSN: 1872-6240
Keywords: P-glycoprotein; brain endothelial cells; blood brain barrier
Academic Unit/Department: Science > Life, Health and Chemical Sciences
Science
Interdisciplinary Research Centre: Innovation, Knowledge & Development research centre (IKD)
Biomedical Research Network (BRN)
Item ID: 17838
Depositing User: Users 9108 not found.
Date Deposited: 28 Jul 2009 16:56
Last Modified: 19 Mar 2014 08:18
URI: http://oro.open.ac.uk/id/eprint/17838
Share this page:

Altmetrics

Scopus Citations

Actions (login may be required)

View Item
Report issue / request change

Policies | Disclaimer

© The Open University   + 44 (0)870 333 4340   general-enquiries@open.ac.uk