Effect of Parathyroid-Hormone-Related Protein on Sodium-Dependent Phosphate Transport in Renal Brush Border Membrane Vesicles in Rats

Abstract

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 K_m and V_max of phosphate transport were identical for the two peptides [hPTHrP(1-34): K_m 27.6 + 0.8 μM, V_max 3.78 ± 0.04 nmol/mg protein, hPTH(1-34): K_m 29.6 ± 0.9 μM, V_max 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 on Na⁺-dependent phosphate transport in brush border membrane vesicles in vitro.

Acute adaptation of renal phosphate transporters in the murine kidney to oral phosphate intake requires multiple signals

“…We also found no differences in the renal abundance of the FGF23 co-receptor, α-Klotho, at any time point and in any group (Figure S3A-F). Due to a possible impact of PTHrp on renal Pi reabsorption, as reported in several species, 29,34,35 we measured the plasma levels of this hormone. PTHrp levels were not altered by Pi gavage, though 4 h after gavage differences between genotypes were observed (Figure 2G-I).…”

Role of Secondary Hyperparathyroidism in the Development of Post-Transplant Acute Tubular Necrosis

“…PTHi stimulates the reabsorption of calcium in the proximal convoluted tubule and stimulates calcium reab sorption against an electrochemical gradient in the distal tubule. After the administration of PTHi in vivo, the Vmax of the sodium-calcium exchanger in subsequently iso lated basolateral membrane vesicles is significantly in creased [37,38], Several studies have demonstrated that l,25(OH)2 cholecalcipherol could normalize intracellu lar calcium through lowering PTHi secretion in uremic patients with secondary hyperparathyroidism [33,39], The reduction in serum PTHi levels in response to 1 ,25(OH)2D i is presumed to be due to an increase in plas ma calcium, and direct suppression of PTHi synthesis secretion, especially after intravenous administration [14,40],…”

Regulation of Hormone-Sensitive Renal Phosphate Transport

“…PTH-related protein (PTHrP) exerts effects similar to the inhibitory action of PTH on renal Pi uptake by isolated brush border membrane vesicles (Muff, Caulfield, & Fischer, 1990;Saito, Hirano, Kubota, Tomino, & Koide, 1993). The biological importance of this action to the normal economy of phosphate is not known.…”