Chronic fluoride ingestion decreases ⁴⁵Ca uptake by rat kidney membranes

High exposures to fluoride (F^-) may occur in environments rich in F^- from natural or industrial sources and from misuse of F^- containing dental care products, particularly by children. Both acute and chronic exposures to elevated levels of F^- have negative effects on several calcium-dependent processes, including kidney glomerular and tubular function. We examined the effect of chronic F^- ingestion on ATP-dependent ⁴⁵Ca uptake by rat kidney membrane vesicles to characterize the mechanism by which high F^- alters Ca⁺⁺ transport in the kidney. Twenty weanling female Sprague-Dawley rats were raised on low-F^- (0.9 mg/L), semi-purified diet with a Ca⁺⁺ concentration of 400 mg/100g diet. Rats were divided into four groups and were fed ad libitum deionized water containing F^- at 0, 10, 50, or 150 mg/L added as NaF for 6 wk. This consumption produced plasma F^- levels of <0.4, 2, 7, or 35 μmol/L, respectively. ATP-dependent ⁴⁵Ca uptake was significantly lower in the 150 mg F^-/L exposure group than in the 0 mg F^- /L controls (P < 0.05). Studies with thapsigargin, a specific inhibitor of the endoplasmic reticulum Ca⁺⁺-pump, showed that the lower uptake was associated with significantly lower activities of both the plasma membrane Ca⁺⁺-pump (P < 0.05, 150 mg F^-/L group versus control) and endoplasmic reticulum Ca⁺⁺-pump (P < 0.05 for both the 50 and 150 mg F^-/L groups versus control). Slot blot analysis of kidney homogenates with specific Ca⁺⁺-pump antibodies showed less (P < 0.05) endoplasmic reticulum Ca⁺⁺- pump protein and plasma membrane Ca⁺⁺-pump protein in all treatment groups than controls. Both Ca⁺⁺-pumps are transport molecules of great importance in the regulation of Ca⁺⁺ homeostasis. Our study suggests that chronic, high F^- ingestion producing high plasma F^- levels may occur in humans and may affect Ca⁺⁺ homeostasis by increasing the turnover or breakdown or decreasing the expression of plasma membrane and endoplasmic reticulum Ca⁺⁺-pump proteins.