Inhibition of P-glycoprotein: rapid ...
Type de document :
Compte-rendu et recension critique d'ouvrage
DOI :
PMID :
Titre :
Inhibition of P-glycoprotein: rapid assessment of its implication in blood-brain barrier integrity and drug transport to the brain by an in vitro model of the blood-brain barrier
Auteur(s) :
Fenart, Laurence [Auteur]
Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique [LBHE]
Buée-Scherrer, Valérie [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Descamps, Laurence [Auteur]
Duhem, Christian [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Poullain, Marie-Gwenaëlle [Auteur]
Cecchelli, Roméo [Auteur]
Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique [LBHE]
Dehouck, Marie-Pierre [Auteur]
Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique [LBHE]
Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique [LBHE]
Buée-Scherrer, Valérie [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Descamps, Laurence [Auteur]
Duhem, Christian [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Poullain, Marie-Gwenaëlle [Auteur]
Cecchelli, Roméo [Auteur]
Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique [LBHE]
Dehouck, Marie-Pierre [Auteur]
Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique [LBHE]
Titre de la revue :
Pharmaceutical Research
Pagination :
993-1000
Éditeur :
American Association of Pharmaceutical Scientists
Date de publication :
1998
ISSN :
0724-8741
Mot(s)-clé(s) en anglais :
P-glycoprotein reversing agents
Anticancer drugs
Cyclosporin A
Brain capillary
Endothelial cells
Coculture
Anticancer drugs
Cyclosporin A
Brain capillary
Endothelial cells
Coculture
Discipline(s) HAL :
Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire
Résumé en anglais : [en]
Purpose. The objective of this work was to asses, in vitro, the passage of P-glycoprotein dependent drugs across brain capillary endothelial cells, when these drugs are associated with a reversing agents. Methods. An in ...
Lire la suite >Purpose. The objective of this work was to asses, in vitro, the passage of P-glycoprotein dependent drugs across brain capillary endothelial cells, when these drugs are associated with a reversing agents. Methods. An in vitro model of the blood-brain barrier consisting of a coculture of brain capillary endothelial cells and astrocytes was used. Results. We demonstrate that P-glycoprotein expression is upregulated by the presence of astrocytes. Uptake in the cells and transport across endothelial cell monolayers of vincristine, cyclosporin A and doxorubicin were studied. Using S9788 or verapamil as reversing agents, we found an increase in vincristine transport across the endothelial cell monolayers. On the other hand, the association of S9788 or verapamil with cyclosporin A failed to increase the transport of this drug. An increase in the transport of doxorubicin from luminal or abluminal compartment was also observed, due to endothelial cell monolayer breakdown. Conclusions. Using this model, it is possible to predict the passage of a P-glycoprotein dependent drug to the brain or its sequestration in brain capillary endothelial cells when this drug is associated with a reversing agent, or its toxicity on the blood-brain barrier integrity.Lire moins >
Lire la suite >Purpose. The objective of this work was to asses, in vitro, the passage of P-glycoprotein dependent drugs across brain capillary endothelial cells, when these drugs are associated with a reversing agents. Methods. An in vitro model of the blood-brain barrier consisting of a coculture of brain capillary endothelial cells and astrocytes was used. Results. We demonstrate that P-glycoprotein expression is upregulated by the presence of astrocytes. Uptake in the cells and transport across endothelial cell monolayers of vincristine, cyclosporin A and doxorubicin were studied. Using S9788 or verapamil as reversing agents, we found an increase in vincristine transport across the endothelial cell monolayers. On the other hand, the association of S9788 or verapamil with cyclosporin A failed to increase the transport of this drug. An increase in the transport of doxorubicin from luminal or abluminal compartment was also observed, due to endothelial cell monolayer breakdown. Conclusions. Using this model, it is possible to predict the passage of a P-glycoprotein dependent drug to the brain or its sequestration in brain capillary endothelial cells when this drug is associated with a reversing agent, or its toxicity on the blood-brain barrier integrity.Lire moins >
Langue :
Anglais
Vulgarisation :
Non
Source :
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