ArticleThe AAPS journal2014
An electrically tight in vitro blood-brain barrier model displays net brain-to-blood efflux of substrates for the ABC transporters, P-gp, Bcrp and Mrp-1.
Article in The AAPS journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
- Review
- Evaluating sex as a biological variable in in vitro blood-brain barrier models: insights from primary mouse brain endothelial cells.Fluids and barriers of the CNS · 2026Article
- Improvement in Transient Agarose Spot (TAS) Cell Migration Assay: Microplate-Based Detection and Evaluation.International journal of molecular sciences · 2025Article
- A cryopreserved andNAM journal · 2025Article
- Selective protection of normal cells from chemotherapy, while killing drug-resistant cancer cells.Oncotarget · 2023Review
- Role of interleukin-6 and interleukin-10 in morphological and functional changes of the blood-brain barrier in hypertriglyceridemia.Fluids and barriers of the CNS · 2023Article
- Transport Mechanisms at the Blood-Brain Barrier and in Cellular Compartments of the Neurovascular Unit: Focus on CNS Delivery of Small Molecule Drugs.Pharmaceutics · 2022Review
- Drug Penetration into the Central Nervous System: Pharmacokinetic Concepts and In Vitro Model Systems.Pharmaceutics · 2021Review
- Human Induced Pluripotent Stem Cell-Derived Brain Endothelial Cells: Current Controversies.Frontiers in physiology · 2021Article
- The blood-brain barrier studied in vitro across species.PloS one · 2021Article
- Recent progress in translational engineered in vitro models of the central nervous system.Brain : a journal of neurology · 2020Review
- IPEC-J2 rMdr1a, a New Cell Line with Functional Expression of Rat P-glycoprotein Encoded by Rat Mdr1a for Drug Screening Purposes.Pharmaceutics · 2020Article
- Modeling blood-brain barrier pathology in cerebrovascular disease in vitro: current and future paradigms.Fluids and barriers of the CNS · 2020Review
- Culture-induced changes in mRNA expression levels of efflux and SLC-transporters in brain endothelial cells.Fluids and barriers of the CNS · 2020Article
- GM1 Oligosaccharide Crosses the Human Blood-Brain Barrier In Vitro by a Paracellular Route.International journal of molecular sciences · 2020Article
- Drug Development for Central Nervous System Diseases Using In vitro Blood-brain Barrier Models and Drug Repositioning.Current pharmaceutical design · 2020Review
- ABC Transporters at the Blood-Brain Interfaces, Their Study Models, and Drug Delivery Implications in Gliomas.Pharmaceutics · 2019Review
- Investigating Maternal Brain Alterations in Preeclampsia: the Need for a Multidisciplinary Effort.Current hypertension reports · 2019Review
- Evaluating the involvement of cerebral microvascular endothelial NaJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Efflux transporters of the ATP-binding cassette superfamily including breast cancer resistance protein (Bcrp/Abcg2), P-glycoprotein (P-gp/Abcb1) and multidrug resistance-associated proteins (Mrp's/Abcc's) are expressed in the blood-brain barrier (BBB). The aim of this study was to investigate if a bovine endothelial/rat astrocyte in vitro BBB co-culture model displayed polarized transport of known efflux transporter substrates. The co-culture model displayed low mannitol permeabilities of 0.95 ± 0.1 · 10(-6) cm·s(-1) and high transendothelial electrical resistances of 1,177 ± 101 Ω·cm(2). Bidirectional transport studies with (3)H-digoxin, (3)H-estrone-3-sulphate and (3)H-etoposide revealed polarized transport favouring the brain-to-blood direction for all substrates. Steady state efflux ratios of 2.5 ± 0.2 for digoxin, 4.4 ± 0.5 for estrone-3-sulphate and 2.4 ± 0.1 for etoposide were observed. These were reduced to 1.1 ± 0.08, 1.4 ± 0.2 and 1.5 ± 0.1, by addition of verapamil (digoxin), Ko143 (estrone-3-sulphate) or zosuquidar + reversan (etoposide), respectively. Brain-to-blood permeability of all substrates was investigated in the presence of the efflux transporter inhibitors verapamil, Ko143, zosuquidar, reversan and MK 571 alone or in combinations. Digoxin was mainly transported via P-gp, estrone-3-sulphate via Bcrp and Mrp's and etoposide via P-gp and Mrp's. The expression of P-gp, Bcrp and Mrp-1 was confirmed using immunocytochemistry. The findings indicate that P-gp, Bcrp and at least one isoform of Mrp are functionally expressed in our bovine/rat co-culture model and that the model is suitable for investigations of small molecule transport.
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