A model of calcium homeostasis in the rat.

Détails

ID Serval
serval:BIB_021B34E5B537
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A model of calcium homeostasis in the rat.
Périodique
American journal of physiology. Renal physiology
Auteur(s)
Granjon D., Bonny O., Edwards A.
ISSN
1522-1466 (Electronic)
ISSN-L
1522-1466
Statut éditorial
Publié
Date de publication
01/11/2016
Peer-reviewed
Oui
Volume
311
Numéro
5
Pages
F1047-F1062
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
We developed a model of calcium homeostasis in the rat to better understand the impact of dysfunctions such as primary hyperparathyroidism and vitamin D deficiency on calcium balance. The model accounts for the regulation of calcium intestinal uptake, bone resorption, and renal reabsorption by parathyroid hormone (PTH), vitamin D3, and Ca(2+) itself. It is the first such model to incorporate recent findings regarding the role of the calcium-sensing receptor (CaSR) in the kidney, the presence of a rapidly exchangeable pool in bone, and the delayed response of vitamin D3 synthesis. Accounting for two (fast and slow) calcium storage compartments in bone allows the model to properly predict the effects of bisphophonates on the plasma levels of Ca(2+) ([Ca(2+)]p), PTH, and vitamin D3 Our model also suggests that Ca(2+) exchange rates between plasma and the fast pool vary with both sex and age, allowing [Ca(2+)]p to remain constant in spite of sex- and age-based hormonal and other differences. Our results suggest that the inconstant hypercalciuria that is observed in primary hyperparathyroidism can be attributed in part to counterbalancing effects of PTH and CaSR in the kidney. Our model also correctly predicts that calcimimetic agents such as cinacalcet bring down [Ca(2+)]p to within its normal range in primary hyperparathyroidism. In addition, the model provides a simulation of CYP24A1 inactivation that leads to a situation reminiscent of infantile hypercalcemia. In summary, our model of calcium handling can be used to decipher the complex regulation of calcium homeostasis.

Pubmed
Création de la notice
07/07/2016 14:54
Dernière modification de la notice
03/03/2018 13:17
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