ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2011
Aryl hydrocarbon receptor-mediated up-regulation of ATP-driven xenobiotic efflux transporters at the blood-brain barrier.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- Internal and Maternal Distribution of Persistent Organic Pollutants in Sea Turtle Tissues: A Meta-Analysis.Environmental science & technology · 2021Pooled it
- Emerging links between gut dysbiosis, aryl hydrocarbon receptor activation, and Parkinson's disease.Communications biology · 2026Review
- Investigating the interaction between aryl hydrocarbon receptor and methotrexate: implications for treatment resistance in rheumatoid arthritis patients.Pharmacological reports : PR · 2026Article
- Schizophrenia as a Disorder of Biological Barriers: A Narrative Review and Potential Interventions.International journal of molecular sciences · 2026Review
- The aryl hydrocarbon receptor and kynurenine pathway: connecting inflammatory bowel disease and depression via the microbiota gut brain axis.Frontiers in neuroscience · 2026Review
- Bioaccumulation and Maternal Transfer of Brominated Flame Retardants in Poultry and the Health Risks from Dietary Exposure.Environment & health (Washington, D.C.) · 2025Article
- The tryptophan metabolic pathway of the microbiome and host cells in health and disease.International immunology · 2024Review
- Receptor-Assisted Nanotherapeutics for Overcoming the Blood-Brain Barrier.Molecular neurobiology · 2024Review
- Six Decades of Dopamine Hypothesis: Is Aryl Hydrocarbon Receptor the New D2?Reports (MDPI) · 2023Review
- Host-Microbiome Interactions: Tryptophan Metabolism and Aromatic Hydrocarbon Receptors after Traumatic Brain Injury.International journal of molecular sciences · 2023Review
- Activation of aryl hydrocarbon receptor (AhR) in Alzheimer's disease: role of tryptophan metabolites generated by gut host-microbiota.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Regulation of P-Glycoprotein in the Brain.International journal of molecular sciences · 2022Review
- Pharmacological blockage of the AHR-CYP1A1 axis: a call for in vivo evidence.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Aryl Hydrocarbon Receptor Mechanisms Affecting Chronic Kidney Disease.Frontiers in pharmacology · 2022Review
- Form and Function of the Vertebrate and Invertebrate Blood-Brain Barriers.International journal of molecular sciences · 2021Review
- Review
- Aryl hydrocarbon receptor: Its roles in physiology.Biochemical pharmacology · 2021Review
- Disruption of small molecule transporter systems by Transporter-Interfering Chemicals (TICs).FEBS letters · 2020Review
- Novel Intrinsic Mechanisms of Active Drug Extrusion at the Blood-Brain Barrier: Potential Targets for Enhancing Drug Delivery to the Brain?Pharmaceutics · 2020Review
- David S. Miller: Scientist, Mentor, Friend-a tribute and thank you.Fluids and barriers of the CNS · 2020Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Many widespread and persistent organic pollutants, e.g., 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), activate the aryl hydrocarbon receptor (AhR), causing it to translocate to the cell nucleus, where it transactivates target genes. AhR's ability to target the blood-brain barrier is essentially unexplored. We show here that exposing isolated rat brain capillaries to 0.05-0.5 nM TCDD roughly doubled transport activity and protein expression of P-glycoprotein, an ATP-driven drug efflux pump and a critical determinant of drug entry into the CNS. These effects were abolished by actinomycin D or cycloheximide or by the AhR antagonists resveratrol and α-naphthoflavone. Brain capillaries from TCDD-dosed rats (1-5 μg/kg, i.p.) exhibited increased transport activity and protein expression of 3 xenobiotic efflux pumps, P-glycoprotein, multidrug resistance-associated protein 2, and breast cancer resistance polypeptide, as well as expression of Cyp1a1 and Cyp1b1, both AhR target genes. Consistent with increased P-glycoprotein expression in capillaries from TCDD-dosed rats, in situ brain perfusion indicated significantly reduced brain accumulation of verapamil, a P-glycoprotein substrate. These findings suggest a new paradigm for the field of environmental toxicology: toxicants acting through AhR to target xenobiotic efflux transporters at the blood-brain barrier and thus reduce brain accumulation of CNS-acting therapeutic drugs.
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Registered trials
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