Sodium Fluoride Increases Intracellular Calcium in Rat Renal Epithelial Cell Line NRK-52E

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In our previous experiment using rats, fluoride was reported to cause renal calcification, whose mechanism was deduced to be due to an increase in parathyroid hormone (PTH) secretion. However fluoride-induced renal calciffication that was independent of PTH has not been nuderstood well in the nephron of fluoride-treated animals. Thus, we examined the effect of sodium fluoride on intracellular calcium mobilization in a normal rat kidney epithelial cell line (NRK-52E cells). The calcium accumulation was found to be remarkably increased by the addition of sodium fluoride (NaF). The elevation of [Ca^<2+>]_i was demonstrated to be due to calcium entry through nifedipine-sensitive calcium channels. In addition, fluoride activates phospholipase C, but inositol 1,4,5-triphosphate (IP_3) didn't induce Ca^<2+> release from the endoplasmic reticulum (ER). Moreover, fluoride alone was deduced to enhance the activity of ER-type Ca^<2+>-ATPase.Finally, on the mechanism of fluoride-induced calcium accumulation in NRK-52E cells, fluoride may activate phospholipase C to generate IP_3 and diacylglycerol, and these increases can be elucidated to induce calcium entry through dihydropiridine-sensitive calcium channels. Moreover, fluoride was found to stimulate calcium accumulation through ER-type Ca^<2+>-ATPase into the endoplasmic reticulum. The elevation of ER-type Ca^<2+>-AT-Pase activity by fluoride was elucidated to operate as a regulatory system to protect against abnormally higher increases in cytosolic calcium concentration via an increase of calcium influx into the endoplasmic reticulum.
公益社団法人日本薬学会の論文
2000-05-01

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Sodium Fluoride Increases Intracellular Calcium in Rat Renal Epithelial Cell Line NRK-52E

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