title: Coordinated control of renal Ca2+ handling.
abstract: Ca2+ homeostasis is an important factor, which is underlined by the numerous clinical symptoms that involve Ca2+ deficiencies. The overall Ca2+ balance is maintained by the concerted action of Ca2+ absorption in the intestine, reabsorption in the kidney, and exchange from bone, which are all under the control of the calciotropic hormones that are released upon a demand for Ca2+. In the kidney, these calciotropic hormones affect active Ca2+ reabsorption, which consists of TRPV5 as the apical entry gate for Ca2+ influx, calbindin-D28K as an intracellular ferry for Ca2+ and, NCX1 and PMCA1b for extrusion of Ca2+ across the basolateral membrane. This review highlights the action of hormones on renal Ca2+ handling and focuses on the coordinated control of the renal Ca2+ transport proteins. Parathyroid hormone stimulates renal Ca2+ handling by regulating active Ca2+ reabsorption on both the genomic and non-genomic level. Estrogens harbor calciotropic hormone characteristics positively regulating the expression of TRPV5, independently of vitamin D. Besides having a strong regulatory effect on the expression of the intestinal Ca2+ transport proteins, vitamin D contributes to the overall Ca2+ balance by enhancing the expression of the Ca2+ transport machinery in the kidney. Dietary Ca2+ is involved in regulating its own handling by controlling the expression of the renal Ca2+ transport proteins. Thus, the magnitude of Ca2+ entry via TRPV5 controls the expression of the other Ca2+ transport proteins underlining the gatekeeper function of this Ca2+ channel in the renal Ca2+ handling.
authors.affiliation: Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: T T
authors.initials: TT
authors.lastname: Lambers
authors.forename: R J M
authors.initials: RJ
authors.lastname: Bindels
authors.forename: J G J
authors.initials: JG
authors.lastname: Hoenderop
mesh_terms: D000042:Absorption / Q000187:drug effects; D000818:Animals; D064092:Calbindin 1; D064026:Calbindins; D002118:Calcium / Q000172:deficiency / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D002136:Calcium, Dietary / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000502:physiology; D027682:Cation Transport Proteins / Q000502:physiology; D004967:Estrogens / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000502:physiology; D053499:Plasma Membrane Calcium-Transporting ATPases; D064030:S100 Calcium Binding Protein G / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000502:physiology; D050916:TRPV Cation Channels / Q000502:physiology; D014807:Vitamin D / Q000502:physiology
chemical_list: C576498:CALB1 protein, human; D064092:Calbindin 1; D064026:Calbindins; D015220:Calcium Channels; D002136:Calcium, Dietary; D027682:Cation Transport Proteins; D004967:Estrogens; D010281:Parathyroid Hormone; D064030:S100 Calcium Binding Protein G; D019831:Sodium-Calcium Exchanger; D050916:TRPV Cation Channels; C492239:TRPV5 protein, human; C110374:sodium-calcium exchanger 1; D014807:Vitamin D; D053499:Plasma Membrane Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium