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 th e present study, we investigated whether CaSR agonists reinforce the decrea se of intracellular free Mg2+ concentration ([Mg2+](i)) induced by extracel lular Mg2+ plus Na+ removal. Interestingly, exposure of NRK-52E renal epith elial 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 a nd protein. By fluorophotometer (with mag-fura 2 fluorescent dye) and atomi c absorption spectrophotometer, we confirmed that activation of CaSR by neo mycin (0.5 mM) or gadolinium (1 mM) reinforced the decrease of [Mg2+](i) in duced 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 in dicate that CaSR monitors extracellular Mg2+ concentration, and probably ca use activation of Na+-independent Mg2+-transport system. (C) 2001 Academic Press.