Díaz-Soto G, Rocher A, García-Rodríguez C, Núñez L, Villalobos C
Endocrinology and Nutrition, Valladolid University Hospital, Valladolid, Spain.
Department of Biochemistry and Molecular Biology and Physiology, University of Valladolid, Valladolid, Spain; Institute of Molecular Biology and Genetics (IBGM), University of Valladolid and National Research Council (CSIC), Valladolid, Spain.
Int Rev Cell Mol Biol. 2016;327:321-369. doi: 10.1016/bs.ircmb.2016.05.004. Epub 2016 Jun 25.
The extracellular calcium-sensing receptor (CaSR) is a unique G protein-coupled receptor (GPCR) activated by extracellular Ca and by other physiological cations including Mg, amino acids, and polyamines. CaSR is the most important master controller of the extracellular Ca homeostatic system being expressed at high levels in the parathyroid gland, kidney, gut and bone, where it regulates parathyroid hormone (PTH) secretion, vitamin D synthesis, and Ca absorption and resorption, respectively. Gain and loss of function mutations in the CaSR are responsible for severe disturbances in extracellular Ca metabolism. CaSR agonists (calcimimetics) and antagonists (calcilytics) are in use or under intense research for treatment of hyperparathyroidism secondary to kidney failure and hypocalcemia with hypercalciuria, respectively. Expression of the CaSR extends to other tissues and systems beyond the extracellular Ca homeostatic system including the cardiovascular system, the airways, and the nervous system where it may play physiological functions yet to be fully understood. As a consequence, CaSR has been recently involved in different pathologies including uncontrolled blood pressure, vascular calcification, asthma, and Alzheimer's disease. Finally, the CaSR has been shown to play a critical role in cancer either contributing to bone metastasis and/or acting as a tumor suppressor in some forms of cancer (parathyroid cancer, colon cancer, and neuroblastoma) and as oncogene in others (breast and prostate cancers). Here we review the role of CaSR in health and disease in calciotropic tissues and others beyond the extracellular calcium homeostatic system.
细胞外钙敏感受体（CaSR）是一种独特的G蛋白偶联受体（GPCR），可被细胞外钙以及其他生理阳离子（包括镁、氨基酸和多胺）激活。CaSR是细胞外钙稳态系统最重要的主控因子，在甲状旁腺、肾脏、肠道和骨骼中高水平表达，在这些部位它分别调节甲状旁腺激素（PTH）分泌、维生素D合成以及钙的吸收和重吸收。CaSR功能的获得性和丧失性突变会导致细胞外钙代谢严重紊乱。CaSR激动剂（拟钙剂）和拮抗剂（钙解剂）分别用于治疗肾衰竭继发的甲状旁腺功能亢进和高钙尿症伴低钙血症，或正处于深入研究阶段。CaSR的表达扩展到细胞外钙稳态系统之外的其他组织和系统，包括心血管系统、气道和神经系统，其在这些系统中可能发挥尚未完全了解的生理功能。因此，CaSR最近已涉及不同的病理状况，包括血压失控、血管钙化、哮喘和阿尔茨海默病。最后，CaSR已被证明在癌症中起关键作用，既有助于骨转移和/或在某些形式的癌症（甲状旁腺癌、结肠癌和神经母细胞瘤）中作为肿瘤抑制因子，而在其他癌症（乳腺癌和前列腺癌）中作为癌基因。在此，我们综述CaSR在钙调节组织以及细胞外钙稳态系统之外的其他组织的健康和疾病中的作用。
