Alterations in renal tubular water transport induced by parathyroid hormone: evidence for both antidiuretic hormone-mediated and independent effects.

Abstract

Abstract The renal tubular effects of PTH and ADH are both mediated by cyclic AMP. Furthermore, both of these agents in pharmacological dosage inhibit phosphate reabsorption in the proximal nephron. Although the effect of ADH on tubular water transport is well documented, the actions of PTH on this tubular function have not been studied. We therefore examined the action of PTH on water reabsorption in conscious, chronically TPTX dogs undergoing maximal steady-state water diuresis. The effects of a supraphysiological amount of the hormone (3 to 5 U/kg) were compared to those produced by a dose of PTH (0.3 to 0.5 U/kg) that restores phosphate excretion to a level seen in normal intact animals. In physiological dosage, PTH increased V from 5.6 ± 0.5 to 6.4 ± 0.5 ml/min (p H 2 O as well as C H 2 O factored for GFR × 100 from 4.26 ± 0.39 to 4.88 ± 0.40 ml/min (p H 2 O and CH2OGFR × 100: 4.70 ± 0.33 → 1.76 ± 0.36 ml/min (p AVP levels rose in three of six animals in which it was measured during high-dose PTH infusion, but the levels were falling at a time when urinary osmolality continued to rise. Furthermore, in vitro, PTH and ADH cross-reacted. That is, PTH largely stimulated cortical cyclic AMP, and ADH increased the production of the nucleotide primarily in the medulla. However, in large dosage PTH activated adenylate cyclase in the medulla, and ADH increased the cortical production of cyclic AMP. When PTH was administered in pharmacological dosage to TPTX, hypophysectomized dogs undergoing maximal water diuresis, there was no change in tubular water transport. We conclude the following from these data. (1) PTH, in pharmacological dosage, has an "ADH-like" effect on renal tubular water transport. (2) This action of PTH does not appear to be consistently related to the measurable release of ADH but (3) seems most likely due to an effect of PTH on medullary adenylate cyclase with subsequent alterations in the permeability of the tubular epithelium to water.