title: Sodium fluoride increases intracellular calcium in rat renal epithelial cell line NRK-52E.
abstract: 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 calcification that was independent of PTH has not been understood 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 [Ca2+]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 (IP3) didn't induce Ca2+ release from the endoplasmic reticulum (ER). Moreover, fluoride alone was deduced to enhance the activity of ER-type Ca2+-ATPase. Finally, on the mechanism of fluoride-induced calcium accumulation in NRK-52E cells, fluoride may activate phospholipase C to generate IP3 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 Ca2+-ATPase into the endoplasmic reticulum. The elevation of ER-type Ca2+-ATPase 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.
authors.affiliation: University of Shizuoka, School of Pharmaceutical Sciences, Department of Environmental Biochemistry and Toxicology, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Murao
authors.forename: N
authors.initials: N
authors.lastname: Sakagami
authors.forename: T
authors.initials: T
authors.lastname: Iguchi
authors.forename: T
authors.initials: T
authors.lastname: Murakami
authors.forename: Y
authors.initials: Y
authors.lastname: Suketa
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002478:Cells, Cultured; D018118:Chloride Channels / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology; D051381:Rats; D012969:Sodium Fluoride / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018118:Chloride Channels; D004095:Dihydropyridines; D010281:Parathyroid Hormone; C038806:1,4-dihydropyridine; D012969:Sodium Fluoride; D010738:Type C Phospholipases; D000252:Calcium-Transporting ATPases; D002118:Calcium