Effect of parathyroid-hormone-related protein on sodium-dependent phosphate transport in renal brush border membrane vesicles in rats. Comparison with parathyroid hormone.

Parathyroid-hormone-related protein (PTHrP) has significant homology with parathyroid hormone (PTH) in the amino-terminal region. We compared the effects of synthetic human PTHrP [hPTHrP(1-34)] on Na(+)-dependent phosphate transport with those of synthetic human PTH [hPTH(1-34)]. Intravenous administration of hPTHrP(1-34) in parathyroidectomized rats caused hypercalcemia, hypophosphatemia and phosphaturia to the same degree as hPTH(1-34). In kinetic studies using renal brush border membrane vesicles, the apparent Km and Vmax of phosphate transport were identical for the two peptides [hPTHrP(1-34): Km 27.6 +/- 0.8 microM, Vmax 3.78 +/- 0.04 nmol/mg protein, hPTH(1-34): Km 29.6 +/- 0.9 microM, Vmax 3.04 +/- 0.90 nmol/mg protein]. Both hPTHrP(1-34) and hPTH(1-34) at a supramaximal dose were equipotent in eliciting a 12-fold increase in cyclic adenosine 3',5'-monophosphate (cAMP) production in the kidney. These results indicate that, in addition to the similar effect of hPTHrP(1-34) and hPTH(1-34) on serum calcium levels and urinary phosphorus and nephrogenous cAMP excretion in vivo, these two peptides have similar effects of Na(+)-dependent phosphate transport in brush border membrane vesicles in vitro.