Polyvalent cation-sensing mechanism increased Na(+)-independent Mg(2+) transport in renal epithelial cells.
Extracellular Ca(2+)/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 Mg(2+) concentration ([Mg(2+)](i)) induced by extracellular Mg(2+) plus Na(+) removal. Interestingly, exposure of NRK-52E renal epithelial cells to increasing extracellular Mg(2+) 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 [Mg(2+)](i) induced by Mg(2+) removal in the cells cultured in 10 mM Mg(2+)-containing medium. The neomycin-induced [Mg(2+)](i) decrease was inhibited by nicardipine (50 microM), but not by verapamil (50 microM) or amiloride (0.1 mM). These results indicate that CaSR monitors extracellular Mg(2+) concentration, and probably cause activation of Na(+)-independent Mg(2+)-transport system.
Ikari
A
A
Department of Environmental Biochemistry and Toxicology, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka, 422-8526, Japan. ikari@u-shizuoka-ken.ac.jp
Nakajima
K
K
Kawano
K
K
Suketa
Y
Y
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002412:Cations; D002460:Cell Line; D004232:Diuretics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000378:metabolism*; D005682:Gadolinium / Q000494:pharmacology; D007668:Kidney / Q000166:cytology* / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism* / Q000494:pharmacology; D009355:Neomycin / Q000494:pharmacology; D009529:Nicardipine / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013054:Spectrophotometry, Atomic; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002412:Cations; D004232:Diuretics; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D000584:Amiloride; D012964:Sodium; D005682:Gadolinium; D014700:Verapamil; D009529:Nicardipine; D009355:Neomycin; D008274:Magnesium; D002118:Calcium