The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Evidence that epithelial glycoprotein 330/megalin mediates uptake of polybasic drugs.
Open accessAbstract
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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Cites
Binding of polymyxin B to the lipid A portion of bacterial lipopolysaccharides
Morrison, D. C., & Jacobs, D. M. (1976) · Immunochemistry · doi:10.1016/0019-2791(76)90181-6 · Cited by 819
Cited by
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Molecular characteristics of insect vitellogenins and vitellogenin receptors
Sappington, T. W., & S. Raikhel, A. (1998) · Insect Biochemistry and Molecular Biology · doi:10.1016/s0965-1748(97)00110-0 · Cited by 521
Identification and Design of Peptides as a New Drug Delivery System for the Brain
Demeule, M., Régina, A., Ché, C., Poirier, J., Nguyen, T., Gabathuler, R., Castaigne, J.-P., & Béliveau, R. (2008) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.107.131318 · Cited by 462
Zlokovic, B. V., Martel, C. L., Matsubara, E., McComb, J. G., Zheng, G., McCluskey, R. T., Frangione, B., & Ghiso, J. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.9.4229 · Cited by 430
Mechanisms of Aminoglycoside Ototoxicity and Targets of Hair Cell Protection
Huth, M. E., Ricci, A. J., & Cheng, A. G. (2011) · International Journal of Otolaryngology · doi:10.1155/2011/937861 · Cited by 393
Metadata
- Authors
- Moestrup, S. K., Cui, S., Vorum, H., Bregengård, C., Bjørn, S. E., Norris, K., Gliemann, J., & Christensen, E. I.
- Venue
- Journal of Clinical Investigation
- Published
- 1995-09-01
- Volume
- 96
- Issue
- 3
- Pages
- 1404-1413
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W1984229760
- Cited by
- 339
- References
- 1
- FWCI
- 5.01
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Moestrup, S. K., Cui, S., Vorum, H., Bregengård, C., Bjørn, S. E., Norris, K., Gliemann, J., & Christensen, E. I. (1995). Evidence that epithelial glycoprotein 330/megalin mediates uptake of polybasic drugs. Journal of Clinical Investigation. https://doi.org/10.1172/jci118176
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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