Polyvalent cation-sensing mechanism increased Na+-independent Mg2+ transport in renal epithelial cells

Extracellular Ca2+/polyvalent cation-sensing receptor (CaSR) is capable of monitoring changes in extracellular polyvalent cation concentrations. In the present study, we investigated whether CaSR agonists reinforce the decrease of intracellular free Mg2+ concentration ([Mg2+](i)) induced by extracellular Mg2+ plus Na+ removal. Interestingly, exposure of NRK-52E renal epithelial cells to increasing extracellular Mg2+ concentrations from 0.8 to 15 mM for 1-2 days resulted in a twofold increase in the levels of CaSR mRNA and protein. By fluorophotometer (with mag-fura 2 fluorescent dye) and atomic absorption spectrophotometer, we confirmed that activation of CaSR by neomycin (0.5 mM) or gadolinium (1 mM) reinforced the decrease of [Mg2+](i) induced by Mg2+ removal in the cells cultured in 10 mM Mg2+-containing medium. The neomycin-induced [Mg2+](i) decrease was inhibited by nicardipine (50 muM), but not by verapamil (50 muM) or amiloride (0.1 mM). These results indicate that CaSR monitors extracellular Mg2+ concentration, and probably cause activation of Na+-independent Mg2+-transport system. (C) 2001 Academic Press.