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  • Differential effects of Vitamin D analogs on calcium transport
  • Nakane M; Ma J; Rose AE; Osinski MA; Wu-Wong JR
  • J Steroid Biochem Mol Biol 2007[Jan]; 103 (1): 84-9
  • It is well known that the efficiency of intestinal active calcium transport is regulated by the Vitamin D receptor pathway and Vitamin D analogs seem to exhibit differential effects on intestinal active calcium transport. To investigate the molecular basis for the difference among Vitamin D analogs, we tested three Vitamin D analogs: 1,25-dihydroxyvitamin D(3), 19-nor-1,25-dihydroxyvitamin D(2), and 1alpha-hydroxyvitamin D(2) ex vivo and in vitro. In 5/6 nephrectomized rat intestinal active calcium transport, 19-nor-1,25-dihydroxyvitamin D(2) did not show a significant effects on intestinal active calcium transport at all the concentrations tested, while 1alpha-hydroxyvitamin D(2) at 0.33 and 0.67 microg/kg and 1,25-dihydroxyvitamin D(3) at 1microg/kg significantly stimulated calcium transport. In Caco-2 cells, 19-nor-1,25-dihydroxyvitamin D(2) did not show a significant effect on calcium transport, while 1,25-dihydroxyvitamin D(3) and 1,25-dihydroxyvitamin D(2) (the active form of 1alpha-hydroxyvitamin D(2)) stimulated calcium transport by 934 and 501% at 0.1microM, respectively. 1,25-Dihydroxyvitamin D(2) potently induced the expression of CALB3 and TRPV6 mRNA with an EC(50) of 0.3 and 1.0nM, whereas 19-nor-1,25-dihydroxyvitamin D(2) was 10-fold less potent than 1,25-dihydroxyvitamin D(2) in inducing CALB3 and TRPV6 mRNA. The three Vitamin D analogs had no significant effect on the expression of PMCA1 mRNA. These Vitamin D analogs did not change the expression of Vitamin D receptor (VDR) up to 10nM, but stimulated CYP24A1 expression in a dose-dependent manner with the potency in the order of 1,25-dihydroxyvitamin D(3)>1,25-dihydroxyvitamin D(2)=19-nor-1,25-dihydroxyvitamin D(2). These results suggest that the differential effect of Vitamin D analogs on stimulating intestinal and Caco-2 calcium transport may be in part due to its different effect on stimulating CALB3 and TRPV6 mRNA expression.
  • |*Ion Transport[MESH]
  • |Animals[MESH]
  • |Caco-2 Cells[MESH]
  • |Calcium/*metabolism[MESH]
  • |Dose-Response Relationship, Drug[MESH]
  • |Humans[MESH]
  • |Male[MESH]
  • |Rats[MESH]
  • |Rats, Sprague-Dawley[MESH]
  • |Reverse Transcriptase Polymerase Chain Reaction[MESH]
  • |Vitamin D/analogs & derivatives/*pharmacology[MESH]





  • *{{pmid17046242}}
    *<b>[http://www.kidney.de/mlpefetch.php?search=17046242 Differential effects of Vitamin D analogs on calcium transport ]</b> J Steroid Biochem Mol Biol 2007; 103(1) ; 84-9 Nakane M; Ma J; Rose AE; Osinski MA; Wu-Wong JR

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    J Steroid Biochem Mol Biol

    84 1.103 2007