1,25-Dihydroxyvitamin D-stimulated calmodulin binding proteins: a sustained effect on distal tubules

Abstract

The tubular localization of 1,25-dihydroxyvitamin D[1,25(OH)2D3]-stimulated calmodulin binding proteins (CaMBP-Ds) in the rat kidney and the specificity of their induction were characterized to better understand renal responses to protracted 1,25(OH)2D3 treatment in vivo. None of the other hormones tested (parathyroid hormone, calcitonin, estradiol-17β, testosterone, progesterone, hydrocortisone, or dexamethasone) stimulated the CaMBP-Ds, whereas maximal 1,25(OH)2D3 stimulation occurred after a 5- to 7-day treatment with 100 ng/day 1,25(OH)2D3. With the exception of the more ubiquitously distributed CaMBP-D150, the CaMBP-Ds were localized in distal, but not proximal, tubule preparations. 1,25(OH)2D3 induction of vitamin D receptors and the CaMBP-Ds was similar with respect to dose-response and time course. Finally, the CaMBP-Ds remained elevated for at least 4 wk after 1,25(OH)2D3 withdrawal. Because the vitamin D-stimulated renal CaMBP-Ds are principally proteins of the distal tubule, they may be associated with renal regulation of Ca2+ homeostasis. The sustained induction of CaMBP-Ds is important in addressing the question of whether their induction is a function of normal Ca2+ homeostasis or a pathophysiological consequence of hypervitaminosis D and hypercalcemia.