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 vine NaF, whereas the renal Na+/K+-ATPase in basolateral membranes showed a dip in activity 3h 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 K-i 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.