The parathyroid calcium receptor: a novel therapeutic target for treating hyperparathyroidism
The parathyroid calcium receptor: a novel therapeutic target for treating hyperparathyroidism
复制标题
甲状旁腺钙受体：治疗甲状旁腺功能亢进症的新靶点
DOI：
10.1007/bf00866757
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发表时间：
1996
影响因子：
3
通讯作者：
J. Fox
中科院分区：
文献类型：
--
作者：
E. Nemeth;M. E. Steffey;J. Fox
甲状旁腺细胞，c细胞和肾中的某些细胞表达细胞表面钙（Ca2+）受体，使这些细胞能够检测和响应细胞外Ca2+浓度的变化。该受体蛋白是G蛋白偶联受体超家族的成员，仅与代谢性谷氨酸受体具有有限的序列同源性。Ca2+受体是调节甲状旁腺激素（PTH）分泌的主要生理机制，在维持全身Ca2+稳态中起关键作用。作为Ca2+受体激动剂的化合物被称为拟钙化剂，因为它们模拟或增强细胞外Ca2+对甲状旁腺细胞功能的影响。NPS R-568是一种小的有机拟钙化化合物，作为一种正变构调节剂，增加Ca2+受体对细胞外Ca2+激活的敏感性。在正常大鼠中，口服NPS R-568可降低血浆PTH和Ca2+水平，并在较高剂量下增加血浆降钙素水平。这两种激素循环水平的变化解释了这种化合物引起的低钙血症。NPS R-568还能有效降低正常人和继发性甲状旁腺功能亢进大鼠血浆PTH水平。钙化模拟化合物的目标Ca2+受体为治疗原发性和继发性甲状旁腺功能亢进提供了一种新的治疗方法。
Parathyroid cells, C-cells, and certain cells in the kidney express a cell surface calcium (Ca2+) receptor which enables these cells to detect and respond to changes in the concentration of extracellular Ca2+. This receptor protein is a member of the G protein-coupled receptor superfamily and shares limited sequence homology only with metabotropic glutamate receptors. The Ca2+ receptor is the primary physiological mechanism regulating the secretion of parathyroid hormone (PTH) and plays a pivotal role in maintaining systemic Ca2+ homeostasis. Compounds that act as Ca2+ receptor agonists are called calcimimetics because they mimic or potentiate the effects of extracellular Ca2+ on parathyroid cell function. NPS R-568 is a small organic calcimimetic compound that acts as a positive allosteric modulator to increase the sensitivity of the Ca2+ receptor to activation by extracellular Ca2+. In normal rats, orally administered NPS R-568 decreases plasma levels of PTH and Ca2+ and, at higher doses, increases plasma levels of calcitonin. The changes in the circulating levels of these two hormones explain the hypocalcemia caused by this compound. NPS R-568 also effectively lowers plasma PTH levels in normal humans and in rat models of secondary hyperparathyroidism. Calcimimetic compounds that target the Ca2+ receptor provide a novel therapeutic approach for treating primary and secondary hyperparathyroidism.
DOI：
10.1210/jcem.76.3.8445032
发表时间：
1993-03
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
S. Khosla;P. Ebeling;A. Firek;M. F. Burritt;P. Kao;H. Heath
通讯作者：
S. Khosla;P. Ebeling;A. Firek;M. F. Burritt;P. Kao;H. Heath
DOI：
10.1073/pnas.92.1.131
发表时间：
1995-01-03
影响因子：
11.1
作者：
RICCARDI, D;PARK, J;HEBERT, SC
通讯作者：
HEBERT, SC
原发性甲状旁腺功能亢进症：发病机制、诊断和治疗的最新进展。
DOI：
--
发表时间：
1992
期刊：
Advances in internal medicine
影响因子：
--
作者：
Heath3rd,H
通讯作者：
Heath3rd,H