ArticleThe Journal of clinical investigation1995
Evidence that epithelial glycoprotein 330/megalin mediates uptake of polybasic drugs.
Article in The Journal of clinical investigation, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
95 citing papers in PubMed, 341 citations in OpenAlex.
- Preliminary clinical study of the effect of ascorbic acid on colistin-associated nephrotoxicity.Antimicrobial agents and chemotherapy · 2015Trial
- Megalin: from structure to function.Nature reviews. Nephrology · 2026Review
- Article
- Megalin (LRP2), prenatal betamethasone, and injury susceptibility in the developing kidney.bioRxiv : the preprint server for biology · 2026Article
- Noncytotoxic polymyxin derivatives enhance antibiotic action against multidrug-resistant Gram-negative bacteria.Antimicrobial agents and chemotherapy · 2025Article
- Megalin: A Sidekick or Nemesis of the Kidney?Journal of the American Society of Nephrology : JASN · 2025Review
- Aprotinin (II): Inhalational Administration for the Treatment of COVID-19 and Other Viral Conditions.International journal of molecular sciences · 2024Review
- Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Radiolabeled 15-mer peptide internalization is mediated by megalin (LRP2 receptor) in a CRISPR/Cas9-based LRP2 knockout human kidney cell model.EJNMMI radiopharmacy and chemistry · 2024Article
- Recent Advances in the Development of Polymyxin Antibiotics: 2010-2023.ACS infectious diseases · 2024Review
- Flucloxacillin worsens while imipenem-cilastatin protects against vancomycin-induced kidney injury in a translational rat model.British journal of pharmacology · 2024Article
- Fluid shear stress-induced changes in megalin trafficking enhance endocytic capacity in proximal tubule cells.Frontiers in physiology · 2024Article
- Dietary supplementation of cystinotic mice by lysine inhibits the megalin pathway and decreases kidney cystine content.Scientific reports · 2023Article
- Peptide-Based Agents for Cancer Treatment: Current Applications and Future Directions.International journal of molecular sciences · 2023Review
- Recoding of Nonsense Mutation as a Pharmacological Strategy.Biomedicines · 2023Review
- Synthesis and Evaluation of Polymyxins Bearing Reductively Labile Disulfide-Linked Lipids.Journal of medicinal chemistry · 2022Article
- Megalin and Vitamin D Metabolism-Implications in Non-Renal Tissues and Kidney Disease.Nutrients · 2022Review
- Mapping Adverse Outcome Pathways for Kidney Injury as a Basis for the Development of Mechanism-Based Animal-Sparing Approaches to Assessment of Nephrotoxicity.Frontiers in toxicology · 2022Article
- Article
- Functional megalin is expressed in renal cysts in a mouse model of adult polycystic kidney disease.Clinical kidney journal · 2021Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycoprotein 330 (gp330) is an endocytic receptor expressed in the renal proximal tubules and some other absorptive epithelia, e.g., in the inner ear. The present study shows that the antifibrinolytic polypeptide, aprotinin, and the nephro- and ototoxic antibiotics, aminoglycosides, and polymyxin B compete for binding of 125I-urokinase-plasminogen activator inhibitor type-1 complexes to purified rabbit gp330. Half maximal inhibition was measured at 4 microM for aprotinin, 50 microM for gentamicin, and 0.5 microM for polymyxin B. Drug binding to gp330 was validated by equilibrium dialysis of [3H] gentamicin-gp330 incubations and binding/uptake studies in rat proximal tubules and gp330-expressing L2 carcinoma cells. Analyses of mutant aprotinins expressed in Saccharomyces cerevisiae revealed that basic residues are essential for the binding to gp330 and renal uptake. The polybasic drugs also antagonized ligand binding to the human alpha 2-macroglobulin receptor. However, the rapid glomerular filtration of the drugs suggests kidney gp330 to be the quantitatively most important target. In conclusion, a novel role of gp330 as a drug receptor is demonstrated. The new insight into the mechanism of epithelial uptake of polybasic drugs might provide a basis for future design of drugs with reduced toxicity.
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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.