Article ; Online: Effects of the EGFR Inhibitor Erlotinib on Magnesium Handling.
Journal of the American Society of Nephrology : JASN
2010 Volume 21, Issue 8, Page(s) 1309–1316
Abstract: ... in TRPM6 current density and tyrosine phosphorylation of EGFR; 0.3 muM erlotinib did not have these effects ... tyrosine kinase inhibitor erlotinib on Mg(2+) homeostasis, however, remains unknown. Here, we injected C57BL/6 ... channels. In summary, erlotinib can influence Mg(2+) handling but its effect on the systemic Mg(2+ ...
| Abstract | 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. |
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| MeSH term(s) | Animals ; ErbB Receptors/antagonists & inhibitors ; ErbB Receptors/biosynthesis ; Erlotinib Hydrochloride ; Magnesium/metabolism ; Mice ; Mice, Inbred C57BL ; Quinazolines/pharmacology ; TRPM Cation Channels/drug effects ; TRPM Cation Channels/physiology | |||||
| Chemical Substances | Quinazolines ; TRPM Cation Channels ; Trpm6 protein, mouse ; Erlotinib Hydrochloride (DA87705X9K) ; ErbB Receptors (EC 2.7.10.1) ; Magnesium (I38ZP9992A) | |||||
| Language | English | |||||
| Publishing date | 2010-07-01 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 1085942-1 | |||||
| ISSN | 1533-3450 ; 1046-6673 | |||||
| ISSN (online) | 1533-3450 | |||||
| ISSN | 1046-6673 | |||||
| DOI | 10.1681/ASN.2009111153 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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