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

Autor: Fenart, Laurence, Buée-Scherrer, Valérie, Descamps, Laurence, Duhem, Christian, Poullain, Marie-Gwenaëlle, Cecchelli, Roméo, Dehouck, Marie-Pierre
Přispěvatelé: Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique (LBHE), Université d'Artois (UA), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, Pharmacocinétique et Métabolisme Préclinique, Sanofi-Aventis, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Jazyk: angličtina
Rok vydání: 1998
Předmět:
Endothelial cells
MESH: Calcium Channel Blockers/pharmacology
MESH: Verapamil/pharmacology
P-glycoprotein reversing agents
Piperidines
MESH: Biological Transport/drug effects
MESH: ATP Binding Cassette Transporter
Subfamily B
Member 1/antagonists & inhibitors
MESH: Animals
MESH: Antineoplastic Agents
Phytogenic/pharmacokinetics
Antibiotics
Antineoplastic
MESH: Endothelium
Vascular/metabolism
Triazines
MESH: ATP Binding Cassette Transporter
Subfamily B
Member 1/biosynthesis
Brain
MESH: Astrocytes/cytology
Calcium Channel Blockers
MESH: Brain/metabolism
MESH: Predictive Value of Tests
MESH: Doxorubicin/pharmacokinetics
MESH: Cattle
Blood-Brain Barrier
Vincristine
Cyclosporine
Immunosuppressive Agents
MESH: Endothelium
Vascular/cytology
MESH: Rats
MESH: Vincristine/pharmacokinetics
MESH: Astrocytes/metabolism
Antineoplastic Agents
MESH: Triazines/pharmacology
Anticancer drugs
MESH: Coculture Techniques
MESH: Cyclosporine/pharmacokinetics
MESH: Antineoplastic Agents/pharmacology
Predictive Value of Tests
Animals
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
ATP Binding Cassette Transporter
Subfamily B
Member 1
MESH: Endothelium
Vascular/drug effects
Biological Transport
MESH: Antibiotics
Antineoplastic/pharmacokinetics
MESH: Brain/blood supply
Antineoplastic Agents
Phytogenic
Coculture Techniques
Coculture
Rats
Brain capillary
Cyclosporin A
Verapamil
MESH: Blood-Brain Barrier/physiology
Doxorubicin
MESH: Piperidines/pharmacology
Astrocytes
Cattle
Endothelium
Vascular
MESH: Immunosuppressive Agents/pharmacokinetics
MESH: Blood-Brain Barrier/drug effects
Zdroj: Pharmaceutical Research
Pharmaceutical Research, American Association of Pharmaceutical Scientists, 1998, 15 (7), pp.993-1000. ⟨10.1023/a:1011913723928⟩
Pharmaceutical Research, 1998, 15 (7), pp.993-1000. ⟨10.1023/a:1011913723928⟩
ISSN: 0724-8741
1573-904X
DOI: 10.1023/a:1011913723928⟩
Popis: International audience; 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.
Databáze: OpenAIRE
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