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).
![[img]](http://oro.open.ac.uk/style/images/fileicons/application_pdf.png)
|
PDF (Accepted Manuscript)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
Download (449kB) |
| DOI (Digital Object Identifier) Link: | https://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 Item |
|---|---|
| Copyright Holders: | 2009 Elsevier |
| ISSN: | 1872-6240 |
| Keywords: | P-glycoprotein; brain endothelial cells; blood brain barrier |
| Academic Unit/School: | Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences Faculty of Science, Technology, Engineering and Mathematics (STEM) |
| 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: | 18 Jul 2017 05:05 |
| URI: | http://oro.open.ac.uk/id/eprint/17838 |
| Share this page: |     |
Altmetrics |
Download history for this item
These details should be considered as only a guide to the number of downloads performed manually. Algorithmic methods have been applied in an attempt to remove automated downloads from the displayed statistics but no guarantee can be made as to the accuracy of the figures.