Goodman William G
Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Semin Nephrol. 2004 Jan;24(1):17-24. doi: 10.1053/j.semnephrol.2003.08.017.
It is now known that variations in extracellular calcium concentration exert diverse physiologic effects in a variety of tissues that are mediated by a calcium-sensing receptor (CaSRs). In parathyroid tissue, the CaSR represents the molecular mechanism by which parathyroid cells detect changes in blood ionized calcium concentration, modulate parathyroid hormone (PTH) secretion accordingly, and thus maintain serum calcium levels within a narrow physiologic range. In the kidney, the CaSR regulates renal calcium excretion and influences the transepithelial movement of water and other electrolytes. More generally, activation of the CaSR represents an important signal transduction pathway in intestine, placenta, brain, and perhaps bone. Some of these actions involve cell cycle regulation, changes that may be relevant to understanding the pathogenesis of parathyroid gland hyperplasia in secondary hyperparathyroidism caused by chronic kidney disease. The CaSR represents an appealing target for therapeutic agents designed to modify parathyroid gland function in vivo, offering the prospect of novel therapies for selected disorders of bone and mineral metabolism. Other receptors capable of responding to extracellular calcium ions also have been identified, but the functional importance of these interactions remains to be determined.
现在已知细胞外钙浓度的变化在多种组织中发挥多种生理作用，这些作用由钙敏感受体（CaSRs）介导。在甲状旁腺组织中，CaSR代表甲状旁腺细胞检测血液中离子钙浓度变化、相应调节甲状旁腺激素（PTH）分泌从而将血清钙水平维持在狭窄生理范围内的分子机制。在肾脏中，CaSR调节肾钙排泄并影响水和其他电解质的跨上皮转运。更普遍地说，CaSR的激活是肠道、胎盘、大脑以及可能还有骨骼中的一条重要信号转导途径。其中一些作用涉及细胞周期调控，这些变化可能与理解慢性肾脏病所致继发性甲状旁腺功能亢进中甲状旁腺增生的发病机制有关。CaSR是旨在体内改变甲状旁腺功能的治疗药物的一个有吸引力的靶点，为选定的骨和矿物质代谢紊乱提供了新疗法的前景。还鉴定出了其他能够对细胞外钙离子作出反应的受体，但这些相互作用的功能重要性仍有待确定。
