Phosphate uptake in chick kidney cells: effects of 1,25(OH)2D3 and 24,25(OH)2D3.
Phosphate homeostasis is controlled in part by absorption from the intestine, and reabsorption in the kidney. While the effect of Vitamin D metabolites on enterocytes is well documented, in the current study we assess selected responses in primary cultures of kidney cells. Time course studies revealed a rapid stimulation of phosphate uptake in cells treated with 1,25(OH)(2)D(3), relative to controls. Dose-response studies indicated a biphasic curve with optimal stimulation at 300 pM 1,25(OH)(2)D(3) and inhibition at 600 pM seco-steroid. Antibody 099--against the 1,25D(3)-MARRS receptor - abolished stimulation by the steroid hormone. Moreover, phosphate uptake was mediated by the protein kinase C pathway. The metabolite 24,25(OH)(2)D(3), which was found to inhibit the rapid stimulation of phosphate uptake in intestinal cells, had a parallel effect in cultured kidney cells. Finally, the 24,25(OH)(2)D(3) binding protein, catalase, was assessed for longer term down regulation. In both intestinal epithelial cells and kidney cells incubated with 24,25(OH)(2)D(3) for 5-24h, both the specific activity of the enzyme and protein levels were decreased relative to controls, while 1,25(OH)(2)D(3) increased both parameters over the same time periods. We conclude that the Vitamin D metabolites have similar effects in both kidney and intestine, and that 24,25(OH)(2)D(3) may have effects at the level of gene expression.
Khanal
R C
RC
Department of Nutrition and Food Sciences, and the Center for Integrated BioSystems, Utah State University, 8700 Old Main Hill, Logan, UT 84322-8700, United States.
Smith
N M
NM
Nemere
I
I
D015650:24,25-Dihydroxyvitamin D 3 / Q000502:physiology*; D000818:Animals; D002117:Calcitriol / Q000502:physiology*; D002374:Catalase / Q000378:metabolism; D002645:Chickens; D007668:Kidney / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010710:Phosphates / Q000378:metabolism*
D010710:Phosphates; D015650:24,25-Dihydroxyvitamin D 3; D002374:Catalase; D002117:Calcitriol