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10.1681/ASN.2009111153

http://scihub22266oqcxt.onion/10.1681/ASN.2009111153
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C2938592!2938592!20595681
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suck abstract from ncbi


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pmid20595681      J+Am+Soc+Nephrol 2010 ; 21 (8): 1309-16
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  • Effects of the EGFR Inhibitor Erlotinib on Magnesium Handling #MMPMID20595681
  • Dimke H; van der Wijst J; Alexander TR; Meijer IM; Mulder GM; van Goor H; Tejpar S; Hoenderop JG; Bindels RJ
  • J Am Soc Nephrol 2010[Aug]; 21 (8): 1309-16 PMID20595681show ga
  • 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 ?M erlotinib inhibited EGF-induced changes in TRPM6 current density and tyrosine phosphorylation of EGFR; 0.3 ?M erlotinib did not have these effects. Furthermore, 30 ?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.
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