Selective drug transport and P-glycoprotein activity in an in vitro blood-brain barrier model

Abstract : To determine whether compounds are able to reach the neural microenvironment, a blood-brain barrier (BBB) co-culture model has been recently developed with bovine brain capillary endothelial cells and newborn rat astrocytes. In this study, the permeability of confluent endothelial cells to various compounds and the functional activity of P-glycoprotein (P-gp), an ATP-dependent pump known to efflux drugs from multidrug-resistant tumoral cells, was assessed. The permeability of the lipophilic compounds imipramine and sulpiride differed in relation to their structure. A good correlation was observed with in vivo brain extraction levels. P-gp activity was estimated by measuring the uptake of [3H]vinblastine by the endothelial cells, with or without verapamil, which is known to reverse drug resistance. Intracellular accumulation of the vinca alkaloid was strongly increased after addition of verapamil, suggesting that P-gp is active in these cells. These results provide further support for the use of the co-culture model of bovine brain endothelial cells and rat astrocytes to screen new centrally active drugs.
Type de document :
Article dans une revue
Toxicology in Vitro, Elsevier, 1995, 9 (4), p. 357-364
Liste complète des métadonnées

https://hal-univ-artois.archives-ouvertes.fr/hal-00546804
Contributeur : Wilfried Déplanques <>
Soumis le : mardi 14 décembre 2010 - 18:19:16
Dernière modification le : lundi 26 mars 2018 - 15:39:57

Identifiants

  • HAL Id : hal-00546804, version 1

Collections

Citation

Baptiste Joly, Olivier Fardel, Roméo Cecchelli, C. Chesné, C. Puozzo, et al.. Selective drug transport and P-glycoprotein activity in an in vitro blood-brain barrier model. Toxicology in Vitro, Elsevier, 1995, 9 (4), p. 357-364. 〈hal-00546804〉

Partager

Métriques

Consultations de la notice

50