PTH-independent regulation of blood calcium concentration by the calcium-sensing receptor
| Autor: | Pascal Houillier, Soline Bourgeois, Bharath Wootla, Dominique Eladari, Renaud de la Faille, Robert H. Dodd, Kamel Laghmani, Corinne Collet, Régine Chambrey, Patrick Bruneval, Hélène Faure, Martial Ruat, Erik Ilsø Christensen, Chantal Mandet, Lydie Cheval, Suresh Krishna Ramakrishnan, Alexandre Loupy |
|---|---|
| Přispěvatelé: | Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Neurology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Service de Néphrologie-Transplantation-Dialyse, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Laboratoire de neurobiologie cellulaire et moléculaire (NBCM), Centre National de la Recherche Scientifique (CNRS), CNRS ERL 8228 - Laboratoire de physiologie rénale et tubulopathies, 75006, Paris, France. (TIR), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Métabolisme et physiologie rénales (ERL 8228), Centre National de la Recherche Scientifique (CNRS)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
MESH: Amino Acids [SDV]Life Sciences [q-bio] 030232 urology & nephrology Pamidronate Parathyroid hormone MESH: Rats Sprague-Dawley MESH: Pamidronate Rats Sprague-Dawley 0302 clinical medicine MESH: Animals Amino Acids Solute Carrier Family 12 Member 1 MESH: Sodium-Potassium-Exchanging ATPase 0303 health sciences Kidney Bone Density Conservation Agents Diphosphonates [CHIM.ORGA]Chemical Sciences/Organic chemistry Chemistry Reabsorption MESH: Naphthalenes General Medicine Parathyroid chief cell MESH: Parathyroid Hormone MESH: Parathyroidectomy medicine.anatomical_structure Parathyroid Hormone Creatinine MESH: Permeability MESH: Calcium MESH: Solute Carrier Family 12 Member 1 Sodium-Potassium-Exchanging ATPase Calcium-sensing receptor MESH: Receptors Calcium-Sensing medicine.medical_specialty MESH: Rats Hypoparathyroidism Sodium-Potassium-Chloride Symporters MESH: Diphosphonates Osteocalcin chemistry.chemical_element MESH: Creatinine Naphthalenes Calcium Permeability MESH: Osteocalcin MESH: Bone Density Conservation Agents 03 medical and health sciences Internal medicine medicine Animals 030304 developmental biology Parathyroidectomy Calcium metabolism MESH: Hypoparathyroidism MESH: Sodium-Potassium-Chloride Symporters urogenital system medicine.disease MESH: Male Rats Endocrinology Loop of Henle Receptors Calcium-Sensing MESH: Loop of Henle |
| Zdroj: | Journal of Clinical Investigation Journal of Clinical Investigation, American Society for Clinical Investigation, 2012, 122 (9), pp.3355-3367. ⟨10.1172/JCI57407⟩ Journal of Clinical Investigation, American Society for Clinical Investigation, 2012, 122 (9), pp.3355-67. ⟨10.1172/JCI57407⟩ Loupy, A, Ramakrishnan, S K, Wootla, B, Chambrey, R, de la Faille, R, Bourgeois, S, Bruneval, P, Mandet, C, Christensen, E I, Faure, H, Cheval, L, Laghmani, K, Collet, C, Eladari, D, Dodd, R H, Ruat, M & Houillier, P 2012, ' PTH-independent regulation of blood calcium concentration by the calcium-sensing receptor ', Journal of Clinical Investigation, vol. 122, no. 9, pp. 3355-3367 . https://doi.org/10.1172/JCI57407 Journal of Clinical Investigation, 2012, 122 (9), pp.3355-3367. ⟨10.1172/JCI57407⟩ |
| ISSN: | 0021-9738 |
| Popis: | International audience; Tight regulation of calcium levels is required for many critical biological functions. The Ca2+-sensing receptor (CaSR) expressed by parathyroid cells controls blood calcium concentration by regulating parathyroid hormone (PTH) secretion. However, CaSR is also expressed in other organs, such as the kidney, but the importance of extraparathyroid CaSR in calcium metabolism remains unknown. Here, we investigated the role of extraparathyroid CaSR using thyroparathyroidectomized, PTH-supplemented rats. Chronic inhibition of CaSR selectively increased renal tubular calcium absorption and blood calcium concentration independent of PTH secretion change and without altering intestinal calcium absorption. CaSR inhibition increased blood calcium concentration in animals pretreated with a bisphosphonate, indicating that the increase did not result from release of bone calcium. Kidney CaSR was expressed primarily in the thick ascending limb of the loop of Henle (TAL). As measured by in vitro microperfusion of cortical TAL, CaSR inhibitors increased calcium reabsorption and paracellular pathway permeability but did not change NaCl reabsorption. We conclude that CaSR is a direct determinant of blood calcium concentration, independent of PTH, and modulates renal tubular calcium transport in the TAL via the permeability of the paracellular pathway. These findings suggest that CaSR inhibitors may provide a new specific treatment for disorders related to impaired PTH secretion, such as primary hypoparathyroidism. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|