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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).
DOI: https://doi.org/10.1016/j.brainres.2009.07.039
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.
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About
- Item ORO ID
- 17838
- Item Type
- Journal Item
- ISSN
- 1872-6240
- Keywords
- P-glycoprotein; brain endothelial cells; blood brain barrier
- Academic Unit or School
-
Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM) - Research Group
-
Innovation, Knowledge & Development research centre (IKD)
Neuroscience Research Group - Copyright Holders
- © 2009 Elsevier
- Depositing User
- Users 9108 not found.