Nephron sites of action of nicotinamide on phosphate reabsorption

The administration of nicotinamide results in urinary phosphate excretions similar to those obtained with pharmacologic doses of parathyroid hormone (PTH). Free-flow micropuncture was performed to localize the nephron site(s) of inhibition of phosphate reabsorption by nicotinamide or PTH in thyroparathyroidectomized (TPTX) rats stabilized on a normal or low phosphate diet. In rats fed a normal phosphate diet phosphaturia was observed following either nicotinamide or PTH treatment. Nicotinamide inhibited phosphate reabsorption in the loop of Henle (pars recta) but not in the accessible proximal tubule. PTH inhibited phosphate reabsorption in both the accessible proximal tubule and the pars recta. In phosphate deprivation, the phosphaturic response to either nicotinamide or PTH was blunted. Although phosphate reabsorption was markedly inhibited in the accessible proximal tubule with both nicotinamide and PTH, subsequent reabsorption in the loop of Henle and distal tubule blunted the phosphaturia. We conclude that nicotinamide primarily inhibits phosphate reabsorption by the pars recta in rats fed a normal phosphate diet, whereas it inhibits phosphate reabsorption by the proximal convoluted tubule in rats fed a low phosphate diet. Furthermore, avid reabsorption of phosphate in the pars recta accounts for the resistance to the phosphaturic effect of nicotinamide or PTH seen in rats fed a low phosphate diet.