Title: Active intestinal calcium transport in the absence of transient receptor potential vanilloid type 6 and calbindin-D-9k
Authors: Benn, Bryan S
Ajibade, Dare
Porta, Angela
Dhawan, Puneet
Hediger, Matthias
Peng, Ji-Bin
Jiang, Yi
Oh, Goo Taeg
Jeung, Eui-Bae
Lieben, Liesbet
Bouillon, Roger
Carmeliet, Geert
Christakos, Sylvia # ×
Issue Date: Jun-2008
Publisher: Endocrine soc
Series Title: Endocrinology vol:149 issue:6 pages:3196-3205
Abstract: To study the role of the epithelial calcium channel transient receptor potential vanilloid type 6 (TRPV6) and the calciumbinding protein calbindin-D-9k in intestinal calcium absorption, TRPV6 knockout (KO), calbindin-D9k KO, and TRPV6/calbindin-D-9k double-KO (DKO) mice were generated. TRPV6 KO, calbindin-D-9k KO, and TRPV6/calbindin-D-9k DKO mice have serum calcium levels similar to those of wild-type (WT) mice (similar to 10 mg Ca2+/dl). In the TRPV6 KO and the DKO mice, however, there is a 1.8-fold increase in serum PTH levels (P < 0.05 compared with WT). Active intestinal calcium transport was measured using the everted gut sac method. Under low dietary calcium conditions there was a 4.1-, 2.9-, and 3.9-fold increase in calcium transport in the duodenum of WT, TRPV6 KO, and calbindin-D-9k KO mice, respectively (n = 8-22 per group; P > 0.1, WT vs. calbindin-D-9k KO, and P < 0.05, WT vs. TRPV6 KO on the low-calcium diet). Duodenal calcium transport was increased 2.1-fold in the TRPV6/calbindin-D-9k DKO mice fed the low-calcium diet (P < 0.05, WT vs. DKO). Active calcium transport was not stimulated by low dietary calcium in the ileum of the WT or KO mice. 1,25-Dihydroxyvitamin D3 administration to vitamin D-deficient null mutant and WT mice also resulted in a significant increase in duodenal calcium transport (1.4- to 2.0-fold, P < 0.05 compared with vitamin D-deficient mice). This study provides evidence for the first time using null mutant mice that significant active intestinal calcium transport occurs in the absence of TRPV6 and calbindin-D-9k, thus challenging the dogma that TRPV6 and calbindin-D-9k are essential for vitamin D-induced active intestinal calcium transport.
ISSN: 0013-7227
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
× corresponding author
# (joint) last author

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