P-Glycoprotein Activity in an in Vitro Blood-Brain Barrier Model

  • B. Joly
  • O. Fardel
  • V. Lécureur
  • C. Chesné
  • C. Puozzo
  • A. Guillouzo
Part of the Advances in Behavioral Biology book series (ABBI, volume 46)


Drug transport across the blood-brain barrier (BBB) is a key step in the treatment of cerebral diseases; it is largely dependent on membrane permeability of brain capillary endothelial cells. In order to investigate the functional features of the BBB in vitro, a coculture model of bovine brain capillary endothelial cells and new-born rat astrocytes has been recently established (Dehouck et al, J. Neurochemistry, 54: 1798–1801, 1990). Using this system, we have analysed brain capillary endothelial cell (BCEC) permeability for vinblastine, an anticancer drug substrate for the multidrug transporter P-glycoprotein (P-gp). Vinblastine endothelial permeability coefficient was found to be low, as for various compounds (i.e. inulin, sucrose, sulpiride), known to poorly accumulate in the brain. In the presence of verapamil, a known inhibitor of P-gp function, vinblastine transfer across BCECs was strongly enhanced. These data therefore suggest that BCECs display P-gp activity that is directly involved in low endothelial permeability of anticancer drugs such as vinblastine.


Endothelial Permeability Coculture Model Multidrug Transporter Brain Capillary Endothelial Cell Mdrl Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Le passage de médicaments à travers la barrière hémato-encéphalique (BHE) est une étape importante dans le traitement de maladies cérébrales; il dépend de la perméabilité membranaire des cellules endothéliales des capillaires cérébraux. Un modèle de coculture de cellules endothéliales de capillaires cérébraux et d’astrocytes de rat nouveaux-nés, a été récemment développé (Dehouck et al, J. Neurochemistry, 54: 1798–1801, 1990), permettant d’étudier les caractéristiques de la BHE in vitro. Nous avons utilisé ce modèle pour apprécier la perméabilité des cellules endothéliales à la vinblastine, un médicament anticancéreux, substrat du transporteur «multidrogue», la P-glycoproteine (P-gp). Nos résultats montrent que le coefficient de perméabilité endothéliale à la vinblastine est faible, tout comme il l’est, pour de nombreux autres composés (inuline, sucrose, sulpiride), connus pour s’accumuler faiblement au niveau cérébral. En présence de vérapamil, un inhibiteur de l’activité de la P-gp, le passage de vinblastine à travers la monocouche de cellules endothéliales est fortement augmenté, ce qui indique que les cellules endothéliales cérébrales, possèdent une activité P-gp pouvant jouer un rôle direct dans la faible perméabilité endothéliale aux médicaments anticancéreux, tels que la vinblastine.


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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • B. Joly
    • 1
    • 2
  • O. Fardel
    • 1
  • V. Lécureur
    • 1
  • C. Chesné
    • 3
  • C. Puozzo
    • 2
  • A. Guillouzo
    • 1
  1. 1.INSERM U 49Hopital PontchaillouRennes cedexFrance
  2. 2.Institut de Recherche Pierre FabreCastresFrance
  3. 3.BiopredicTechnopole Atalante VillejeanRennesFrance

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