title: Chronic fluoride ingestion decreases 45Ca uptake by rat kidney membranes.
abstract: 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 micromol/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.
authors.affiliation: Department of Oral Biology, Medical College of Georgia, School of Dentistry, Augusta, Georgia 30912-1129, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Borke
authors.forename: G M
authors.initials: GM
authors.lastname: Whitford
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology; D000284:Administration, Oral; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000493:pharmacokinetics*; D002132:Calcium Radioisotopes; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002462:Cell Membrane / Q000201:enzymology; D004721:Endoplasmic Reticulum / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005459:Fluorides / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects; D007668:Kidney / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D014867:Water
chemical_list: D002132:Calcium Radioisotopes; D004791:Enzyme Inhibitors; D014867:Water; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; D005459:Fluorides; D002118:Calcium