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. 2008 Dec 16;105(50):19655-9.
doi: 10.1073/pnas.0810761105. Epub 2008 Dec 10.

TRPV6 is not required for 1alpha,25-dihydroxyvitamin D3-induced intestinal calcium absorption in vivo

Affiliations

TRPV6 is not required for 1alpha,25-dihydroxyvitamin D3-induced intestinal calcium absorption in vivo

Galina D Kutuzova et al. Proc Natl Acad Sci U S A. .

Abstract

The requirement for TRPV6 for vitamin D-dependent intestinal calcium absorption in vivo has been examined by using vitamin D-deficient TRPV6 null mice and littermate wild-type mice. Each of the vitamin D-deficient animals received each day for 4 days 50 ng of 1,25-dihydroyvitamin D(3) in 0.1 ml of 95% propylene glycol:5% ethanol vehicle or vehicle only. Both the wild-type and TRPV6 null mice responded equally well to 1,25-dihydroxyvitamin D(3) in increasing intestinal calcium absorption. These results, along with our microarray data, demonstrate that TRPV6 is not required for vitamin D-induced intestinal calcium absorption and may not carry out a significant role in this process. These and previous results using calbindin D9k null mutant mice illustrate that molecular events in the intestinal calcium absorption process in response to the active form of vitamin D remain to be defined.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Serum calcium concentration in wild-type and TRPV6 mutant male (A) and female (B) mice after 1,25-(OH)2D3 administration. Five- to six-month-old vitamin D3-deficient wild-type and KO mice were injected i.p. daily with 50 ng 1,25-(OH)2D3 in 95% propylene glycol/5% ethanol or vehicle (95% propylene glycol/5% ethanol) for 3 consecutive days. Mice were bled on day 4 via their maxillary veins to determine serum calcium level. Data are expressed as mean ± SD (n = 8–12). Blood samples were processed according to the method described in Material and Methods. *, Difference with control (vehicle) is statistically significant (P < 0.005).
Fig. 2.
Fig. 2.
1α,25-Dihydroxyvitamin D3-stimulated 45Ca absorption in small intestine of wild-type and TRPV6 KO male (A) and female (B) vitamin D-deficient mice. TRPV6 wild-type and TRPV6 KO mice were injected i.p. with 50 ng 1,25-(OH)2D3 or vehicle (95% propylene glycol/5% ethanol) for 4 consecutive days. Twenty-four hours after the fourth injection, mice were dosed with 0.5 μCi 45CaCl2 via gastric gavage and killed 45 min later. Intestines were harvested, and the radioactivity remaining in intestines was measured by scintillation counting. The percentage of 45CaCl2 absorbed was calculated as described in the Methods section. All values are reported as mean ± SD (n = 8–9 for male mice and n = 9–12 for female mice). *, Significantly different from vehicle control (P < 0.001).
Fig. 3.
Fig. 3.
TRPV6 expression fold increase over control in rat duodenum by microarray analysis (Materials and Methods) 3 h after IV injection of 90 ng 1,25-(OH)2D3 or 700 ng E analog per kg of body weight. The bars represent SEM for 6 observations. The fold increase is significant for both compounds (P < 0.01).
Fig. 4.
Fig. 4.
Serum Ca2+ level in rats (n = 6) after IV injection of (A) 90 ng 1,25-(OH)2D3 or (B) 700 ng E analog per kg of body weight. *, Significantly different from value measured before administration of 1,25-(OH)2D3 (P < 0.01). There were no changes observed in the E analog-treated group.

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