TY - JOUR
T1 - 1,25-Dihydroxyvitamin D3 inhibits Na+-dependent phosphate transport in osteoblastic cells
AU - Green, J.
AU - Luong, K. V.Q.
AU - Kleeman, C. R.
AU - Ye, L. H.
AU - Chaimovitz, C.
PY - 1993/1/1
Y1 - 1993/1/1
N2 - In the present work we investigated the influence of vitamin D3 metabolites on Na+-dependent phosphate (P(i)) transport in the clonal osteoblastic cell line UMR-106. The vitamin D3 metabolite 1,25- dihydroxyvitamin D3 [1,25(OH)2D3] dose-dependently inhibited P(i) transport with a half-maximal concentration of ~5 x 10-11 M. The effect of 1,25(OH)2D3 was first observed after 8 h of preincubation period. Inhibition of phosphate uptake was relatively specific for the 1,25(OH)2D3 analogue of vitamin D3. The potency order was 1,25(OH)2D3 >> 24,25- dihydroxyvitamin D3 > 25-[3H]hydroxyvitamin D3. Kinetically, 1,25(OH)2D3 decreased the maximal velocity of the phosphate uptake system, whereas the affinity for phosphate was unaffected. Activation of protein kinase C (PKC) in UMR-106 cells stimulated Na+-dependent P(i) transport. Nonetheless, the inhibitory effect of 1,25(OH)2D3 on P(i) transport was not related to downregulation of PKC. Chemical determination of intracellular P(i) showed a 50% reduction after 24-h preincubation with 10-8 M 1,25(OH)2D3. We conclude that 1,25(OH)2D3 inhibits Na+-dependent phosphate transport in osteoblastic cells. This in turn leads to intracellular P(i) depletion. The physiological implication of this phenomenon on the effects of vitamin D on osteoblasts in situ is discussed.
AB - In the present work we investigated the influence of vitamin D3 metabolites on Na+-dependent phosphate (P(i)) transport in the clonal osteoblastic cell line UMR-106. The vitamin D3 metabolite 1,25- dihydroxyvitamin D3 [1,25(OH)2D3] dose-dependently inhibited P(i) transport with a half-maximal concentration of ~5 x 10-11 M. The effect of 1,25(OH)2D3 was first observed after 8 h of preincubation period. Inhibition of phosphate uptake was relatively specific for the 1,25(OH)2D3 analogue of vitamin D3. The potency order was 1,25(OH)2D3 >> 24,25- dihydroxyvitamin D3 > 25-[3H]hydroxyvitamin D3. Kinetically, 1,25(OH)2D3 decreased the maximal velocity of the phosphate uptake system, whereas the affinity for phosphate was unaffected. Activation of protein kinase C (PKC) in UMR-106 cells stimulated Na+-dependent P(i) transport. Nonetheless, the inhibitory effect of 1,25(OH)2D3 on P(i) transport was not related to downregulation of PKC. Chemical determination of intracellular P(i) showed a 50% reduction after 24-h preincubation with 10-8 M 1,25(OH)2D3. We conclude that 1,25(OH)2D3 inhibits Na+-dependent phosphate transport in osteoblastic cells. This in turn leads to intracellular P(i) depletion. The physiological implication of this phenomenon on the effects of vitamin D on osteoblasts in situ is discussed.
KW - alanine
KW - bone mineralization
KW - collagen
KW - protein kinase C
KW - sodium-phosphate cotransport
UR - http://www.scopus.com/inward/record.url?scp=0027503125&partnerID=8YFLogxK
U2 - 10.1152/ajpcell.1993.264.2.c287
DO - 10.1152/ajpcell.1993.264.2.c287
M3 - Article
C2 - 8447362
AN - SCOPUS:0027503125
VL - 264
SP - C287-C295
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 1522-1563
IS - 2 33-2
ER -