ArticleMolecular and cellular biology2004
Mrp4 confers resistance to topotecan and protects the brain from chemotherapy.
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers.
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Who cites it
149 citing papers in PubMed, 411 citations in OpenAlex.
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- Differential Selectivity of Human and Mouse ABCC4/Abcc4 for Arsenic Metabolites.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Metabolite transport across central nervous system barriers.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Review
- Contribution of Direct Cerebral Vascular Transport in Brain Substance Clearance.Aging and disease · 2024Review
- Efflux ABC transporters in drug disposition and their posttranscriptional gene regulation by microRNAs.Frontiers in pharmacology · 2024Review
- Molecular Mechanisms of Organic Anion Transporting Polypeptide-Mediated Organic Anion Clearance at the Blood-Cerebrospinal Fluid Barrier.Molecular pharmacology · 2023Article
- Functional Evaluation of P-gp and Bcrp at the Murine Blood-Cerebrospinal Fluid Barrier.Pharmaceutical research · 2023Article
- The Role of Biological Rhythms in New Drug Formulations to Cross the Brain Barriers.International journal of molecular sciences · 2023Review
- Regulation of ABC transporters by sex steroids may explain differences in drug resistance between sexes.Journal of physiology and biochemistry · 2023Review
- Maternal and Fetal Expression of ATP-Binding Cassette and Solute Carrier Transporters Involved in the Brain Disposition of Drugs.Advances in experimental medicine and biology · 2023Article
- The choroid plexus: a missing link in our understanding of brain development and function.Physiological reviews · 2023Review
- Evaluation of Blood-CSF Barrier Transport by Quantitative Real Time Fluorescence Microscopy.Pharmaceutical research · 2022Article
- Transporter Regulation in Critical Protective Barriers: Focus on Brain and Placenta.Pharmaceutics · 2022Review
- Current Chemical, Biological, and Physiological Views in the Development of Successful Brain-Targeted Pharmaceutics.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- The Daily Expression of ABCC4 at the BCSFB Affects the Transport of Its Substrate Methotrexate.International journal of molecular sciences · 2022Article
- Blood-Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke.International journal of molecular sciences · 2022Review
- Choroid Plexus and Drug Removal Mechanisms.The AAPS journal · 2021Review
- Changes in Gene Expression Profiling and Phenotype in Aged Multidrug Resistance Protein 4-Deficient Mouse Retinas.Antioxidants (Basel, Switzerland) · 2021Article
- Generation of Knockout and Transgenic Zebrafish to Characterize Abcc4 Functions in Detoxification and Efflux of Lead.International journal of molecular sciences · 2021Article
89 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
The role of the multidrug resistance protein MRP4/ABCC4 in vivo remains undefined. To explore this role, we generated Mrp4-deficient mice. Unexpectedly, these mice showed enhanced accumulation of the anticancer agent topotecan in brain tissue and cerebrospinal fluid (CSF). Further studies demonstrated that topotecan was an Mrp4 substrate and that cells overexpressing Mrp4 were resistant to its cytotoxic effects. We then used new antibodies to discover that Mrp4 is unique among the anionic ATP-dependent transporters in its dual localization at the basolateral membrane of the choroid plexus epithelium and in the apical membrane of the endothelial cells of the brain capillaries. Microdialysis sampling of ventricular CSF demonstrated that localization of Mrp4 at the choroid epithelium is integral to its function in limiting drug penetration into the CSF. The topotecan resistance of cells overexpressing Mrp4 and the polarized expression of Mrp4 in the choroid plexus and brain capillary endothelial cells indicate that Mrp4 has a dual role in protecting the brain from cytotoxins and suggest that the therapeutic efficacy of central nervous system-directed drugs that are Mrp4 substrates may be improved by developing Mrp4 inhibitors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.