Effects of the EGFR Inhibitor Erlotinib on Magnesium Handling
| Autor: | Sabine Tejpar, René J. M. Bindels, Jenny van der Wijst, Harry van Goor, Gemma M. Mulder, Joost G. J. Hoenderop, Todd Alexander, Henrik Dimke, Inez M.J. Meijer |
|---|---|
| Přispěvatelé: | Groningen Institute for Organ Transplantation (GIOT), Groningen Kidney Center (GKC) |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
EXPRESSION
medicine.medical_specialty TARCEVA CP-358 774 medicine.drug_class TRPM6 Membrane transport and intracellular motility [NCMLS 5] TRPM Cation Channels RECEPTOR TYROSINE KINASE Tyrosine-kinase inhibitor Receptor tyrosine kinase chemistry.chemical_compound Erlotinib Hydrochloride Mice SECONDARY HYPOCALCEMIA CHANNEL Internal medicine CP-358 medicine Animals Magnesium Epidermal growth factor receptor HYPOMAGNESEMIA GeneralLiterature_REFERENCE(e.g. dictionaries encyclopedias glossaries) Renal disorder [IGMD 9] EGFR inhibitors biology Reabsorption Tyrosine phosphorylation Cell Biology General Medicine CANCER respiratory tract diseases ErbB Receptors DEFICIENCY Mice Inbred C57BL Endocrinology Basic Research chemistry Nephrology biology.protein Quinazolines Erlotinib Receptor Epidermal Growth Factor medicine.drug |
| Zdroj: | Dimke, H A, van der Wijst, J, Alexander, T R, Meijer, I M J, Mulder, G M, van Goor, H, Tejpar, S, Hoenderop, J G & Bindels, R J 2010, ' Effects of the EGFR Inhibitor Erlotinib on Magnesium Handling ' Journal of the American Society of Nephrology, vol. 21, no. 8, pp. 1309-16 . https://doi.org/10.1681/ASN.2009111153 Journal of the American Society of Nephrology, 21, 1309-16 Journal of the American Society of Nephrology, 21(8), 1309-1316. AMER SOC NEPHROLOGY Journal of the American Society of Nephrology, 21, 8, pp. 1309-1316 Journal of the American Society of Nephrology, 21, 8, pp. 1309-16 Journal of the American Society of Nephrology, 21, 1309-1316 |
| ISSN: | 1046-6673 |
| DOI: | 10.1681/ASN.2009111153 |
| Popis: | Contains fulltext : 88763.pdf (Publisher’s version ) (Open Access) A mutation in pro-EGF causes isolated hypomagnesemia, and monoclonal antibodies targeting the extracellular domain of the EGF receptor (EGFR) affect epithelial Mg(2+) transport. The effect of the EGFR tyrosine kinase inhibitor erlotinib on Mg(2+) homeostasis, however, remains unknown. Here, we injected C57BL/6 mice with erlotinib for 23 days and observed a small but significant decrease in serum Mg(2+) concentrations at days 16 and 23, but the fractional excretion of Mg(2+) remained unchanged after 23 days. Semiquantitative immunohistochemical evaluation did not reveal detectable changes in renal expression of transient receptor potential melastatin 6 (TRPM6) protein, the channel that mediates Mg(2+) reabsorption. Patch clamp analysis in TRPM6-expressing cells demonstrated that 30 muM erlotinib inhibited EGF-induced changes in TRPM6 current density and tyrosine phosphorylation of EGFR; 0.3 muM erlotinib did not have these effects. Furthermore, 30 muM erlotinib inhibited EGF-stimulated increases in the mobile fraction of endomembrane TRPM6 channels. In summary, erlotinib can influence Mg(2+) handling but its effect on the systemic Mg(2+) concentration seems less potent than that observed with antibody-based EGFR inhibitors. These data suggest that typical human dosages of erlotinib are unlikely to severely affect serum Mg(2+) concentrations. 01 augustus 2010 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|