Physiology and pathophysiology of the calcium-sensing receptor in the kidney

被引:242
作者
Riccardi, Daniela [2 ]
Brown, Edward M. [1 ]
机构
[1] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA
[2] Cardiff Univ, Sch Biosci, Cardiff CF10 3AX, Wales
基金
英国生物技术与生命科学研究理事会;
关键词
proximal tubule; thick ascending limb; distal convoluted tubule; collecting duct; 1,25-dihydroxyvitamin D-3; parathyroid hormone; hypercalcemia; hypocalcemia; hypercalciuria; calcimimetic; hyperparathyroidism; inactivating mutation; activating mutation; polymorphism; familial hypocalciuric hypercalcemia; neonatal severe primary hyperparathyroidism; autosomal dominant hypoparathyroidism; FAMILIAL HYPOCALCIURIC HYPERCALCEMIA; NEONATAL SEVERE HYPERPARATHYROIDISM; AUTOSOMAL-DOMINANT HYPOCALCEMIA; EXTRACELLULAR CA2+-SENSING RECEPTOR; THICK ASCENDING LIMBS; PARATHYROID-HORMONE SECRETION; VASOPRESSIN-ELICITED WATER; BONE-MINERAL DENSITY; VITAMIN-D METABOLISM; APICAL K+ CHANNELS;
D O I
10.1152/ajprenal.00608.2009
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Riccardi D, Brown EM. Physiology and pathophysiology of the calcium-sensing receptor in the kidney. Am J Physiol Renal Physiol 298: F485-F499, 2010. First published November 18, 2009; doi:10.1152/ajprenal.00608.2009.-The extracellular calcium-sensing receptor (CaSR) plays a major role in the maintenance of a physiological serum ionized calcium (Ca2+) concentration by regulating the circulating levels of parathyroid hormone. It was molecularly identified in 1993 by Brown et al. in the laboratory of Dr. Steven Hebert with an expression cloning strategy. Subsequent studies have demonstrated that the CaSR is highly expressed in the kidney, where it is capable of integrating signals deriving from the tubular fluid and/or the interstitial plasma. Additional studies elucidating inherited and acquired mutations in the CaSR gene, the existence of activating and inactivating autoantibodies, and genetic polymorphisms of the CaSR have greatly enhanced our understanding of the role of the CaSR in mineral ion metabolism. Allosteric modulators of the CaSR are the first drugs in their class to become available for clinical use and have been shown to treat successfully hyperparathyroidism secondary to advanced renal failure. In addition, preclinical and clinical studies suggest the possibility of using such compounds in various forms of hypercalcemic hyperparathyroidism, such as primary and lithium-induced hyperparathyroidism and that occurring after renal transplantation. This review addresses the role of the CaSR in kidney physiology and pathophysiology as well as current and in-thepipeline treatments utilizing CaSR-based therapeutics.
引用
收藏
页码:F485 / F499
页数:15
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