4A). Similarly, induction of TRPV6 gene expression was observed from low concentrations of calcitriol (590 pmol/L and ≥2480 pmol/L). Calbindin-D9k gene expression was unchanged by the administration of calcitriol or eldecalcitol (Fig. 4B). In the kidneys, TRPV5 mRNA expression Selleckchem Tyrosine Kinase Inhibitor Library was significantly elevated at the highest concentration

of eldecalcitol (15,800 pmol/L) and at high concentrations of calcitriol (≥1170 pmol/L) (Fig. 4C). Calbindin-D28k mRNA was increased at the higher blood concentrations of eldecalcitol (≥7520 pmol/L) and calcitriol (≥1170 pmol/L) (Fig. 4D). In bone, blood concentrations of calcitriol correlated with RANKL and FGF-23 gene expression; however, only the highest Osimertinib concentration of eldecalcitol (15,800 pmol/L) induced RANKL and FGF-23 gene expression (Fig. 4E). Blood concentration of calcitriol

correlated with VDR gene expression in the kidneys and bone (Fig. 5B and C), but calcitriol did not affect VDR gene expression in the intestine (Fig. 5A). Induction of VDR gene expression in the intestine and kidneys were associated with increasing concentration of eldecalcitol in the blood (Fig. 5A and B). In bone, significant induction of VDR gene expression was observed only at the highest concentration of eldecalcitol (Fig. 5C). Taken together, these results show that, in comparison to calcitriol, relatively higher concentrations of eldecalcitol in the blood were required to stimulate expression of vitamin D target genes in the kidneys (VDR, TRPV5, and calbindin-D28k) and bone (VDR, RANKL, and FGF-23). In order to compare the true biological activity of calcitriol and eldecalcitol in vivo, the blood concentration required to elicit a 50% response in each activity was calculated from the raw data above. The ratio of biological activity was obtained by dividing

the 50% response concentration of calcitriol by that of eldecalcitol. Based on these calculations, eldecalcitol was approximately 1/4 to 1/7 as active as calcitriol in increasing serum calcium and FGF-23, in stimulating urinary calcium excretion, and in suppressing Oxymatrine plasma PTH ( Table 1). Eldecalcitol was approximately 1/3 to 1/8 as active as calcitriol in stimulating expression of target genes in the kidneys (VDR, TRPV5, and calbindin-D28k) and bone (VDR, FGF-23, and RANKL). The biological activities of eldecalcitol in increasing intestinal TRPV6 and VDR gene expression were comparable to those of calcitriol ( Fig. 4 and Fig. 5). The half-life of eldecalcitol in the blood is much longer than it is for calcitriol [23]. Although eldecalcitol strongly induces CYP24A1 in the intestine and kidneys [24], eldecalcitol itself is hardly degraded by CYP24A1 [25]. At the same time, eldecalcitol strongly suppresses CYP27B1 in the kidneys.