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Na/P(i) cotransporter (Npt2) gene disruption increases duodenal calcium absorption and expression of epithelial calcium channels 1 and 2.
Pflugers Arch 2002; 444(5):670-6PA

Abstract

Mice homozygous for the disrupted type-II Na/P(i) cotransporter gene (Npt2(-/-)) exhibit hypophosphataemia, increased serum concentration of 1,25-dihydroxyvitamin D (1,25-(OH)(2)D) and calcium (Ca) and elevated urinary Ca excretion. To determine whether the hypercalcaemia and hypercalciuria are secondary to 1,25-(OH)(2)D-stimulated intestinal Ca absorption, we examined the effect of Npt2 gene disruption on serum Ca and urinary Ca excretion after an overnight fast, and on duodenal Ca absorption. We also compared the duodenal expression of the epithelial Ca channels, ECaC1 and ECaC2, and calbindinD(9K) mRNAs, relative to that of beta-actin mRNA, in Npt2(+/+) and Npt2(-/-) mice. Both serum Ca and urine Ca/creatinine were significantly decreased in Npt2(-/-) mice after an overnight fast and were no longer different from that in wild-type mice. Absorption of (45)Ca from isolated duodenal segments in vivo and (45)Ca appearing in the plasma were significantly increased in Npt2(-/-) compared with Npt2(+/+) mice. In addition, the duodenal abundance of ECaC1, ECaC2 and calbindinD(9K) mRNAs was significantly elevated in mutant mice relative to that in wild-type mice. In contrast, both duodenal Ca absorption and ECaC1 and ECaC2 mRNA abundance were lower in mice with X-linked hypophosphataemia (Hyp) than in normal littermates. In summary, we provide evidence for increased duodenal Ca absorption in Npt2(-/-) mice and suggest a role for ECaC1, ECaC2 and calbindinD(9K) in mediating this response.

Authors+Show Affiliations

Department of Pediatrics, McGill University-Montreal Children's Hospital Research Institute, 2300 Tupper Street, Montreal, Quebec H3H 1P3, Canada. mdht@debelle.mcgill.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12194021

Citation

Tenenhouse, Harriet S., et al. "Na/P(i) Cotransporter (Npt2) Gene Disruption Increases Duodenal Calcium Absorption and Expression of Epithelial Calcium Channels 1 and 2." Pflugers Archiv : European Journal of Physiology, vol. 444, no. 5, 2002, pp. 670-6.
Tenenhouse HS, Gauthier C, Martel J, et al. Na/P(i) cotransporter (Npt2) gene disruption increases duodenal calcium absorption and expression of epithelial calcium channels 1 and 2. Pflugers Arch. 2002;444(5):670-6.
Tenenhouse, H. S., Gauthier, C., Martel, J., Hoenderop, J. G., Hartog, A., Meyer, M. H., ... Bindels, R. J. (2002). Na/P(i) cotransporter (Npt2) gene disruption increases duodenal calcium absorption and expression of epithelial calcium channels 1 and 2. Pflugers Archiv : European Journal of Physiology, 444(5), pp. 670-6.
Tenenhouse HS, et al. Na/P(i) Cotransporter (Npt2) Gene Disruption Increases Duodenal Calcium Absorption and Expression of Epithelial Calcium Channels 1 and 2. Pflugers Arch. 2002;444(5):670-6. PubMed PMID: 12194021.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Na/P(i) cotransporter (Npt2) gene disruption increases duodenal calcium absorption and expression of epithelial calcium channels 1 and 2. AU - Tenenhouse,Harriet S, AU - Gauthier,Claude, AU - Martel,Josée, AU - Hoenderop,Joost G J, AU - Hartog,Anita, AU - Meyer,Martha H, AU - Meyer,Ralph A,Jr AU - Bindels,René J M, Y1 - 2002/07/16/ PY - 2002/03/08/received PY - 2002/04/24/revised PY - 2002/04/25/accepted PY - 2002/8/24/pubmed PY - 2003/3/4/medline PY - 2002/8/24/entrez SP - 670 EP - 6 JF - Pflugers Archiv : European journal of physiology JO - Pflugers Arch. VL - 444 IS - 5 N2 - Mice homozygous for the disrupted type-II Na/P(i) cotransporter gene (Npt2(-/-)) exhibit hypophosphataemia, increased serum concentration of 1,25-dihydroxyvitamin D (1,25-(OH)(2)D) and calcium (Ca) and elevated urinary Ca excretion. To determine whether the hypercalcaemia and hypercalciuria are secondary to 1,25-(OH)(2)D-stimulated intestinal Ca absorption, we examined the effect of Npt2 gene disruption on serum Ca and urinary Ca excretion after an overnight fast, and on duodenal Ca absorption. We also compared the duodenal expression of the epithelial Ca channels, ECaC1 and ECaC2, and calbindinD(9K) mRNAs, relative to that of beta-actin mRNA, in Npt2(+/+) and Npt2(-/-) mice. Both serum Ca and urine Ca/creatinine were significantly decreased in Npt2(-/-) mice after an overnight fast and were no longer different from that in wild-type mice. Absorption of (45)Ca from isolated duodenal segments in vivo and (45)Ca appearing in the plasma were significantly increased in Npt2(-/-) compared with Npt2(+/+) mice. In addition, the duodenal abundance of ECaC1, ECaC2 and calbindinD(9K) mRNAs was significantly elevated in mutant mice relative to that in wild-type mice. In contrast, both duodenal Ca absorption and ECaC1 and ECaC2 mRNA abundance were lower in mice with X-linked hypophosphataemia (Hyp) than in normal littermates. In summary, we provide evidence for increased duodenal Ca absorption in Npt2(-/-) mice and suggest a role for ECaC1, ECaC2 and calbindinD(9K) in mediating this response. SN - 0031-6768 UR - https://www.unboundmedicine.com/medline/citation/12194021/Na/P_i__cotransporter__Npt2__gene_disruption_increases_duodenal_calcium_absorption_and_expression_of_epithelial_calcium_channels_1_and_2_ L2 - https://dx.doi.org/10.1007/s00424-002-0865-2 DB - PRIME DP - Unbound Medicine ER -