Differences in Effects of Amino-Terminal and Intact Parathyroid Hormone on Calcium, Phosphate, and cAMP Excretion by the Isolated Perfused Rat Kidney

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Abstract
Urinary cAMP (UcAMP) reflects activation of renal adenylate cyclase by parathyroid hormone (PTH). UcAMP excretion and the phosphaturic, anticalciuretic responses to bovine PTH by a stable isolated perfused rat kidney were compared. Dose-response curves were obtained for two synthetic amino-terminal [1–34] PTH preparations and three highly purified intact [1–84] PTH preparations. With all preparations, anticalciuria occurred at lower concentrations ( < 10-10 M) than those needed to produce a significant increase in UcAMP excretion or phosphate excretion. Maximal decreases in calcium clearance with [1–34] PTH were independent of concentrations between 10-10 and 10-7 M whereas cAMP and phosphate increased sigmoidally at PTH concentrations above 10-10 M. The two synthetic [1–34] PTH preparations had identical anticalciuretic and phosphaturic dose-response curves despite their significantly different effects on cAMP excretion. Intact [1–84] PTH concentration-response curves were identical to those of [1–34] PTH at concentrations less than 3×10-9 M. At higher concentrations, phosphaturia was greater and anticalciuria blunted compared to [1–34] PTH. These latter changes were associated with natriuresis and kaliuresis, effects not seen with [1–34] PTH. The isolated kidney may be a useful model for further studies of PTH action and also constitutes a bioassay system to evaluate hormone potency.