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).
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| 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: | 09 Mar 2014 07:42 |
| URI: | http://oro.open.ac.uk/id/eprint/17838 |
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