Structural Determinants of the Renal Tubular Activity of Vitamin D 3 Derivatives: Studies with 1α-Hydroxy,24 R,25-Dihydroxy,and 1α,24 R,25-Trihydroxy Vitamin D 3

Abstract

Summary

The acute effects of 24R,25-DHCC, lα,24R,25-THCC, and lα-HCC on the renal handling of phosphate, calcium, and sodium were evaluated in the TPTX dog which had been mildly volume expanded and infused with vasopression to establish a phosphaturia. Both lα-HCC and lα,24R,25-THCC when given intravenously in a dosage of 0.625 μg produced a significant decrease in urinary phosphate excretion. Percentage phosphate excretion decreased by 30 and 28%, respectively (P < 0.05, < 0.01). Since there was no alteration in renal hemodynamics or in the filtered load of this ion, the data suggest a direct action of these compounds on renal tubular transport mechanisms. No change in the urinary excretion of either calcium or sodium was observed following the administration of the two vitamin D₃ derivatives. 24R,25-DHCC was without effect on the renal handling of all three ions.

When previous experimental findings regarding the renal actions of 25-HCC and lα,25-DHCC are considered, the data suggest that the 1-hydroxyl grouping is required for the metabolites of vitamin D to influence phosphate transport at the renal tubular level. It appears that a sterically unhindered 25-hydroxyl group is necessary in order for the vitamin D₃ derivatives to act on the reabsorption of either calcium or sodium.