The extracellular calcium-sensing receptor: Its role in health and disease

被引:158
|
作者
Brown, EM
Pollak, M
Hebert, SC
机构
[1] Brigham & Womens Hosp, Dept Med, Div Endocrine Hypertens, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA
[3] Vanderbilt Univ, Sch Med, Div Renal, Nashville, TN 37235 USA
来源
ANNUAL REVIEW OF MEDICINE | 1998年 / 49卷
关键词
parathyroid; kidney; calcium homeostasis; familial hypocalciuric hypercalcemia; autosomal dominant hypocalcemia;
D O I
10.1146/annurev.med.49.1.15
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The recent cloning of an extracellular calcium (Ca-0(2+))-sensing receptor (CaR) from parathyroid, kidney and other cell types has clarified the mechanisms through which Ca-0(2+) exerts its direct actions on various cells and tissues. In the parathyroid, the CaR mediates the inhibitory effects of Ca-0(2+) on parathyroid hormone (PTH) secretion and likely on expression of the PTH gene and parathyroid cellular proliferation. In the kidney, the receptor mediates direct inhibition of the reabsorption of divalent cations in the cortical thick ascending limb, and it likely underlies the inhibitory actions of hypercalcemia on the urinary-concentrating mechanism in the medullary thick ascending limb and inner medullary collecting duct. The identification of inherited diseases of Ca-0(2+)-sensing that arise from mutations in the CaR gene has proven, by genetic means, the central role of the CaR in mineral ion homeostasis and the importance of the receptor in regulating the parathyroid and kidney. An allosteric CaR agonist ("calcimimetic") is currently being tested for the treatment of primary hyperparathyroidism, and CaR-based therapeutics will likely be applicable to other disorders in which CaRs are under-or overactive. Thus the discovery of the CaR and its associated diseases has documented that Ca-0(2+) plays an essential role as an extracellular first messenger, in addition to serving its better recognized role as an intracellular second messenger.
引用
收藏
页码:15 / 29
页数:15
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