Chronic fluoride ingestion decreases Ca-45 uptake by rat kidney membranes

High exposures to fluoride (F-) may occur in environments rich in F- from n atural or industrial sources and from misuse of F--containing dental care p roducts, particularly by children. Both acute and chronic exposures to elev ated levels of F- have negative effects on several calcium-dependent proces ses, including kidney glomerular and tubular function. We examined the effe ct of chronic F- ingestion on ATP-dependent Ca-45 uptake by rat kidney memb rane vesicles to characterize the mechanism by which high F- alters Ca+ + t ransport in the kidney. Twenty weanling female Sprague-Dawley rats were rai sed on low-F- (0.9 mg/L), semi-purified diet with a Cafe concentration of 4 00 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 mu mol /L, respectively. ATP-dependent Ca-45 uptake was significantly lower in the 150 mg F-/L exposure group than in the 0 mg F-/L controls (P < 0.05). Stud ies with thapsigargin, a specific inhibitor of the endoplasmic reticulum Ca + +-pump, showed that the lower uptake was associated with significantly lo wer 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 k idney homogenates with specific Ca+ +-pump antibodies showed less (P < 0.05 ) endoplasmic reticulum Ca+ +-pump protein and plasma membrane Ca+ +-pump p rotein in all treatment groups than controls. Both Ca+ +-pumps are transpor t molecules of great importance in the regulation of Ca+ + homeostasis. Our study suggests that chronic, high F- ingestion producing high plasma F- le vels 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.