22-Oxacalcitriol does not interfere with parathyroid hormone-induced phosphaturia or cyclic-AMP excretion

The vitamin D analogue, 22-oxacalcitriol [22-oxa-1,25(OH)₂ vitamin D₃], has pleiotropic effects similar to or greater than calcitriol but has markedly fewer calcemic and phosphatemic effects. To test the hypothesis that the lesser phosphatemic effect of 22-oxacalcitriol is due, at least in part, to a lack of interference with the phosphaturic effect of parathyroid hormone, acute clearance experiments were performed in parathyroidectomized rats receiving continuous 1-34 parathyroid hormone (PTH) infusion together with 22-oxacalcitriol (200 pmol · 100 g body weight^-1 · min^-1) or vehicle. In contrast to the previously reported inhibitory effect of calcitriol on PTH-induced phosphaturia, fractional excretion of phosphorus increased similarly in both groups, from 0.05 ± 0.01 to 0.26 ± 0.02 (p < 0.01) in the vehicle-infused animals and from 0.04 ± 0.01 to 0.24 ± 0.02 (p < 0.01) in the 22-oxacalcitriol-treated rats (p between groups not significant [n.s.]). Urinary cyclic AMP excretion also increased similarly, from 45.5 ± 5.2 to 101.6 ± 21.6 (p < 0.01) and from 45.4 ± 5.6 to 102.6 ±16.7 pmoUmin (p < 0.01), respectively (p between groups n.s.). In search for a nongenomic mechanism that might account for the disparate effects of 22-oxacalcitriol and calcitriol, OK cells, which are reminiscent of the mammalian proximal tubule cell, were stimulated with calcitriol and 22-oxacalcitriol and free intracellular calcium concentration was determined. At high concentrations, calcitriol caused a dose-dependent increase in [Ca²⁺]_i; 22-oxacalcitriol had no effect on [Ca²⁺], at any concentration. The results indicate that, in contrast to calcitriol, 22-oxacalcitriol neither interferes with the phosphaturic response to PTH nor alters the PTH-induced increase in urinary cAMP excretion, and does not generate a rise in free intracellular calcium.