Regulation of vitamin D metabolism by calcium and phosphate ions in isolated renal tubules.
The acute and long-term effects of Ca2+ and Pi on vitamin D metabolism were studied in vitro with isolated renal tubules from vitamin D-deficient and vitamin D-supplemented chicks. Ca2+ depletion, achieved by isolating renal tubules in Ca2+-free buffers, led to suppression of 1 alpha-hydroxylase activity. Re-introduction of Ca2+ during incubation caused an acute stimulation of this enzyme. This stimulatory effect of Ca2+ was prevented by prior treatment of Ca2+-depleted renal tubules for 6 h with 1,25-dihydroxycholecalciferol. Ca2+ and Pi produced marked acute affects on 1 alpha-hydroxylase activity, which persisted for the whole 8 h experimental period, in Ca2+-depleted renal tubules from vitamin D-deficient chicks. The effects of either ion were influenced by the concentration of the other. However, the effects of these ions could not be reproduced in either Ca2+-depleted renal tubules from vitamin D-supplemented chicks or in renal tubules from vitamin D-deficient chicks, isolated in Ca2+-containing buffers. Isolation of renal tubules from vitamin D-supplemented chicks in Ca2+-containing buffers and subsequent incubation for 8 h in the presence of increased [Ca2+] led to a modest but statistically significant suppression of 1 alpha-hydroxylase and stimulation of 24-hydroxylase activity. It is concluded that the acute effects of Ca2+ and Pi on 1 alpha-hydroxylase activity of Ca2+-depleted renal tubules from vitamin D-deficient chicks are not regulatory but the results of the experimental conditions. In contrast the long-term effects of Ca2+ on both hydroxylases of renal tubules from vitamin D-supplemented chicks may be of physiological significance.
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002645:Chickens; D003577:Cytochrome P-450 Enzyme System; D004100:Dihydroxycholecalciferols / Q000494:pharmacology; D066298:In Vitro Techniques; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010710:Phosphates / Q000494:pharmacology*; D013250:Steroid Hydroxylases / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism*; D014808:Vitamin D Deficiency / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
D004100:Dihydroxycholecalciferols; D010710:Phosphates; D014807:Vitamin D; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002118:Calcium