ArticleBritish journal of pharmacology2016
Blood-brain and retinal barriers show dissimilar ABC transporter impacts and concealed effect of P-glycoprotein on a novel verapamil influx carrier.
Article in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 59 citations in OpenAlex.
- Hydroxysafflor Yellow A for Diabetic Retinopathy: A Critical Review of Retinal Neurovascular Mechanisms and Systemic-to-Ocular Pharmacokinetic Barriers.Antioxidants (Basel, Switzerland) · 2026Review
- Perinatal Maturation of Drug Transporters and Claudin-5 at the Blood-Brain Barrier.CNS neuroscience & therapeutics · 2025Article
- Mechanistic insights into P-glycoprotein ligand transport and inhibition revealed by enhanced molecular dynamics simulations.Computational and structural biotechnology journal · 2024Article
- Investigating how HIV-1 antiretrovirals differentially behave as substrates and inhibitors of P-glycoprotein via molecular dynamics simulations.Computational and structural biotechnology journal · 2024Article
- Cadmium transport by mammalian ATP-binding cassette transporters.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024Review
- Association between retinopathy and risk of dementia in a general Japanese population: the Hisayama Study.Scientific reports · 2024Article
- Nanostructured Lipid Carriers Mediated Drug Delivery to Posterior Segment of Eye and theirCurrent pharmaceutical biotechnology · 2024Review
- Dissimilar Effect of P-Glycoprotein and Breast Cancer Resistance Protein Inhibition on the Distribution of Erlotinib to the Retina and Brain in Humans and Mice.Molecular pharmaceutics · 2023Article
- Morphine pharmacokinetics and opioid transporter expression at the blood-retina barrier of male and female mice.Frontiers in pharmacology · 2023Article
- Modelling the Human Blood-Brain Barrier in Huntington Disease.International journal of molecular sciences · 2022Article
- Bile Duct Ligation Impairs Function and Expression of Mrp1 at Rat Blood-Retinal Barrier via Bilirubin-Induced P38 MAPK Pathway Activations.International journal of molecular sciences · 2022Article
- Morphine Accumulates in the Retina Following Chronic Systemic Administration.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Review
- Pharmacophore-Based Discovery of Substrates of a Novel Drug/Proton-Antiporter in the Human Brain Endothelial hCMEC/D3 Cell Line.Pharmaceutics · 2022Article
- ABCG2/BCRP transport mechanism revealed through kinetically excited targeted molecular dynamics simulations.Computational and structural biotechnology journal · 2022Article
- RNA-Seq Analysis Reveals an Essential Role of the Tyrosine Metabolic Pathway and Inflammation in Myopia-Induced Retinal Degeneration in Guinea Pigs.International journal of molecular sciences · 2021Article
- Balance of Drug Residence and Diffusion in Lacrimal Fluid Determine Ocular Bioavailability in In Situ Gels Incorporating Tranilast Nanoparticles.Pharmaceutics · 2021Article
- Comparative transcriptome analysis of inner blood-retinal barrier and blood-brain barrier in rats.Scientific reports · 2021Article
- Transient Receptor Potential Vanilloid in the Brain Gliovascular Unit: Prospective Targets in Therapy.Pharmaceutics · 2021Review
- Correlation of Technical and Adjunctive Factors with Quantitative Tumor Reduction in Children Undergoing Selective Ophthalmic Artery Infusion Chemotherapy for Retinoblastoma.AJNR. American journal of neuroradiology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe respective impact and interplay between ABC (P-glycoprotein/P-gp/Abcb1a, BCRP/ABCG2, MRP/ABCC) and SLC transporter functions at the blood-brain barrier (BBB) and blood-retinal barriers (BRB) are incompletely understood. EXPERIMENTAL APPROACH: We measured the initial cerebral and retinal distribution of selected ABC substrates by in situ carotid perfusion using P-gp/Bcrp knockout mice and chemical ABC/SLC modulation strategies. P-gp, Bcrp, Mrp1 and Mrp4 were studied by confocal retina imaging. KEY
resultsChemical or physical disruption of P-gp increased [(3) H]-verapamil transport by ~10-fold at the BBB and ~1.5-fold at the BRB. [(3) H]-Verapamil transport involved influx-mediated by an organic cation clonidine-sensitive/diphenhydramine-sensitive proton antiporter at both barriers; this effect was unmasked when P-gp was partially or fully inhibited/disrupted at the BBB. Studies of [(3) H]-mitoxantrone and [(3) H]-zidovudine transport suggested, respectively, that Bcrp efflux was less involved at the BRB than BBB, whereas Mrps were significantly and similarly involved at both barriers. Confocal imaging showed that P-gp and Bcrp were expressed in intra-retinal vessels (inner BRB/iBRB) but absent from the blood/basal membrane of cells of the retinal pigment epithelium (outer BRB/oBRB/RPE) where, in contrast, Mrp1 and Mrp4 were localized. CONCLUSIONS AND IMPLICATIONS: P-gp, Bcrp, Mrp1 and Mrp4 are differentially expressed at the outer and inner BRB, resulting in an altered ability to limit substrate distribution at the retina as compared with the BBB. [(3) H]-Verapamil distribution is not P-gp-specific and involves a proton antiporter at both the BBB and BRB. However, this transport is concealed by P-gp at the BBB, but not at the BRB, where P-gp activity is reduced.
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