The calcium-sensing receptor controls parathyroid hormone (PTH) secretion and thereby sets blood calcium concentration. However, it is unclear whether the CaSR in other tissues can modulate blood calcium concentration in a PTH-independent manner. We investigated the role of CaSR in thyroparathyroidectomized (carried out under peritoneal injection of a mixture (0.1ml/100 g body weight) of ketamine (10% v/v) and xylazine (5% v/v)), PTH-supplemented, and in aparathyroid rats. Chronic inhibition of CaSR selectively increased renal tubular calcium absorption and blood calcium concentration without altering bone Ca release or intestinal Ca absorption. In the kidney, CaSR was found to be mostly expressed in the thick ascending limb of the loop of Henle (TAL). CaSR inhibitors selectively increased calcium reabsorption and paracellular pathway permeability in in vitro microperfused TAL. Opposite results were obtained by chronic activation of the CaSR. We conclude that extraparathyroid CaSR is a determinant of blood calcium concentration independent of PTH, mainly by modulating renal tubular calcium transport. CaSR inhibitors may provide a new specific treatment of disorders related to impaired PTH secretion, such as hypoparathyroidism.
University College London (2011) Proc Physiol Soc 24, SA02
Research Symposium: PTH-independent regulation of blood calcium concentration by the calcium-sensing receptor
A. Loupy2,3, S. Ramakrishnan2,3, B. Wootla2,3, R. Chambrey2,3, S. Bourgeois10, R. de la Faille2,4, P. Bruneval5, C. Mandet5, E. Christensen6, H. Faure7, L. Cheval4, K. Laghmani2,3, C. Collet9, D. Eladari1,2, R. H. Dodd8, M. Ruat7, P. Houillier1,2
1. Departement de Physiologie, UniversitÚ Paris Descartes, Paris, France. 2. INSERM UMRS 872, Paris, France. 3. UniversitÚ Pierre et Marie Curie, Paris, France. 4. CNRS ERM 7226, Paris, France. 5. DÚpartement de Pathologie, Hopital EuropÚen Georges Pompidou, Paris, France. 6. Department of Anatomy, University of Aarhus, Aarhus, Denmark. 7. CNRS UPR 9040, Gif sur Yvette, France. 8. CNRS UPR 2301, Gif sur Yvette, France. 9. Departement de Biochimie et Biologie MolÚculaire, Hopital LariboisiÞre, Paris, France. 10. Physiology Institute, University of Zurich, Zurich, Switzerland.
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