Journal
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
Volume 21, Issue 8, Pages 1309-1316Publisher
AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2009111153
Keywords
-
Categories
Funding
- The Netherlands Organization for Scientific Research (ZonMw) [9120 6110, 91208026]
- European Science Foundation
- Dutch Kidney Foundation [C03 6017, C05 4106, C06 2166]
Ask authors/readers for more resources
A mutation in pro-EGF causes isolated hypomagnesemia, and monoclonal antibodies targeting the extracellular domain of the EGF receptor (EGFR) affect epithelial Mg2+ transport. The effect of the EGFR tyrosine kinase inhibitor erlotinib on Mg2+ homeostasis, however, remains unknown. Here, we injected C57BL/6 mice with erlotinib for 23 days and observed a small but significant decrease in serum Mg2+ concentrations at days 16 and 23, but the fractional excretion of Mg2+ 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 Mg2+ reabsorption. Patch clamp analysis in TRPM6-expressing cells demonstrated that 30 mu M erlotinib inhibited EGF-induced changes in TRPM6 current density and tyrosine phosphorylation of EGFR, 0.3 mu M erlotinib did not have these effects. Furthermore, 30 mu M erlotinib inhibited EGF-stimulated increases in the mobile fraction of endomembrane TRPM6 channels. In summary, erlotinib can influence Mg2+ handling but its effect on the systemic Mg2+ 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 Mg2+ concentrations.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available