Effect of fluoride on the activities of the Na+/glucose cotransporter and Na+/K(+)-ATPase in brush border and basolateral membranes of rat kidney (in vitro and in vivo).
In this study, renal Na+/K(+)-ATPase activity was demonstrated to be strongly suppressed prior to the glucosuria caused by a fluoride dose (NaF 35 mg/kg, i.p.), and the 50% suppression of the enzyme activity was almost at the same dose of NaF, about 30 mg/kg, i.p. to rats. In the rats, renal Na+/glucose cotransporter activity in brush border membranes was not affected by in vivo NaF, whereas the renal Na+/K(+)-ATPase in basolateral membranes showed a dip in activity 3 h after NaF treatment of the whole animal. Moreover, it was suggested from experiments with inhibitors of calphostin C and KT5720 that protein kinase C, but not protein kinase A, may play an important role in the suppression of Na+/K(+)-ATPase following the administration of fluoride to rats. Na+/glucose cotransporter was fairly insensitive to NaF, being competitively inhibited with a Ki of about 100 mM, whereas Na+/K(+)-ATPase was much more sensitive, with a Ki of about 2 mM. From these results, the elevation of urinary glucose excretion after a single dose of fluoride was deduced to be due to suppression of the renal Na+/K(+)-ATPase activity by a direct and/or secondary action of fluoride, rather than of the corresponding Na+/glucose cotransporter activity.
Suketa
Y
Y
University of Shizuoka School of Pharmaceutical Sciences, Department of Environmental Biochemistry and Toxicology, Japan.
Suzuki
K
K
Taki
T
T
Itoh
Y
Y
Yamaguchi
M
M
Sakurai
T
T
Tanishita
Y
Y
D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D005459:Fluorides / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008871:Microvilli / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects* / Q000378:metabolism
D009004:Monosaccharide Transport Proteins; D000254:Sodium-Potassium-Exchanging ATPase; D005459:Fluorides