title: Localization and function of the renal calcium-sensing receptor.
abstract: The ability to monitor changes in the ionic composition of the extracellular environment is a crucial feature that has evolved in all living organisms. The cloning and characterization of the extracellular calcium-sensing receptor (CaSR) from the mammalian parathyroid gland in the early 1990s provided the first description of a cellular, ion-sensing mechanism. This finding demonstrated how cells can detect small, physiological variations in free ionized calcium (Ca(2+)) in the extracellular fluid and subsequently evoke an appropriate biological response by altering the secretion of parathyroid hormone (PTH) that acts on PTH receptors expressed in target tissues, including the kidney, intestine, and bone. Aberrant Ca(2+) sensing by the parathyroid glands, as a result of altered CaSR expression or function, is associated with impaired divalent cation homeostasis. CaSR activators that mimic the effects of Ca(2+) (calcimimetics) have been designed to treat hyperparathyroidism, and CaSR antagonists (calcilytics) are in development for the treatment of hypercalciuric disorders. The kidney expresses a CaSR that might directly contribute to the regulation of many aspects of renal function in a PTH-independent manner. This Review discusses the roles of the renal CaSR and the potential impact of pharmacological modulation of the CaSR on renal function.
authors.affiliation: Division of Pathophysiology and Repair, School of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX, UK.
authors.forename: Daniela
authors.initials: D
authors.lastname: Riccardi
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, Via Orabona 4, 70125, Bari, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Valenti
mesh_terms: D000818:Animals; D006801:Humans; D007668:Kidney / Q000502:physiology*; D053040:Nephrolithiasis / Q000209:etiology; D009399:Nephrons / Q000502:physiology; D044169:Receptors, Calcium-Sensing / Q000502:physiology*
chemical_list: D044169:Receptors, Calcium-Sensing