Specific inhibition of rat renal Na+/phosphate cotransport by picolinamide

Nicotinamide is both a precursor for NAD synthesis and an inhibitor of intracellular NAD hydrolysing enzymes. Overnight treatment of rats with nicotinamide causes dose-dependent inhibition of the Na+/phosphate cotransporter in the renal brush border membrane. Picolinamide is an isomer of nicotinamide that cannot be used for NAD synthesis. Picolinamide was used in the present study to explore the possibility that inhibition of Na+/phosphate cotransport may be related to inhibition of NAD hydrolyzing enzymes. Overnight treatment of rats with picolinamide, administered as a single injection (4 mmol/kg), inhibited Na+/phosphate cotransport by isolated renal brush border membrane vesicles. Like nicotinamide, the inhibition by picolinamide occurred in thyroparathyroidectomized rats, was specific for Na+/phosphate cotransport and was accompanied by a decrease in the apparent Vmax. In contrast to nicotinamide, there was only a small increase (1.5-fold) in renal cortical NAD content after picolinamide treatment. Direct incubation of isolated proximal tubules with thymidine, a potent inhibitor of NAD hydrolysis by intracellular enzymes, produced no change in Na+/phosphate cotransport. Thus, specific inhibition of renal Na+/phosphate cotrasport by picolinamide in vivo is unlikely due to inhibition of NAD hydrolyzing enzymes. It is suggested, based on data from in vitro studies, that a cyclic AMP-dependent mechanism may be involved.