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.
Saito
K
K
Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Hirano
K
K
Kubota
M
M
Tomino
Y
Y
Koide
H
H
D000818:Animals; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D010280:Parathyroid Glands / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D016105:Parathyroidectomy; D010446:Peptide Fragments / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism*; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D019379:Teriparatide
D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D010710:Phosphates; D011506:Proteins; D019379:Teriparatide; D012964:Sodium