RENAL BRUSH-BORDER MEMBRANE NA+-SULFATE COTRANSPORT - STIMULATION BY THYROID-HORMONE

The present study was undertaken to examine the interaction of phosphonoformic acid (PFA) with the Na+-sulfate cotransporter and the effect of thyroid hormone (triiodothyronine; T3) on Na+-dependent sulfate transport and Na+-dependent PFA binding in mouse renal brush-border membrane vesicles. PFA inhibits Na+-dependent sulfate transport in a competitive manner [apparent inhibitory constant (K(i)) = 4.3 +/- 1.1 mM]. T3 administered in pharmacological doses significantly stimulates Na+-dependent sulfate transport in renal brush-border membranes compared with vehicle-treated controls. Although T3 has no effect on Na+-dependent glucose transport, T3 also stimulates Na+-dependent phosphate transport. Kinetic studies demonstrate that T3 increases the apparent maximal velocity (V(max)) for Na+-sulfate cotransport without changing the apparent Michaelis constant (K(m)). T3 does not significantly affect either Na+-dependent PFA binding or the phosphate- and sulfate-displaceable components of Na+-dependent PFA binding. Finally, Na+-dependent brush-border membrane sulfate transport is unchanged in phosphate-deprived mice that exhibit increased Na+-phosphate cotransport and in X-linked Hyp mice that exhibit impaired Na+-phosphate cotransport. The present results demonstrate that 1) PFA is a competitive inhibitor of Na+-sulfate cotransport, 2) T3 stimulates Na+-dependent sulfate, as well as Na+-dependent phosphate transport, but has no effect on PFA binding, and 3) phosphate deprivation and the X-linked Hyp mutation do not influence Na+-sulfate cotransport. Our data indicate that PFA, a competitive inhibitor of Na+-dependent phosphate transport, interacts in a similar manner with the Na+-sulfate cotransporter of renal brush-border membranes and that T3, at least at pharmacological concentrations, is an important regulator of both Na+-dependent anion transport systems.