Differences in effects of amino-terminal and intact parathyroid hormone on calcium, phosphate, and cAMP excretion by the isolated perfused rat kidney.

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 (less than 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 x 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.