Mancilla E E, De Luca F, Baron J
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Mol Genet Metab. 1998 Jul;64(3):198-204. doi: 10.1006/mgme.1998.2716.
The Ca2+-sensing receptor (CaR) is a member of the seven-transmembrane domain, G-protein-coupled receptor superfamily. It is expressed in parathyroid, kidney, and other tissues. In parathyroid, activation of the CaR by extracellular Ca2+ negatively regulates the secretion of parathyroid hormone. In the the thick ascending limb of Henle's loop, receptor activation decreases renal reabsorption of Ca2+. Heterozygous inactivating mutations of the CaR cause familial benign hypocalciuric hypercalcemia while homozygous inactivating mutations cause neonatal severe hyperparathyroidism. Conversely, activating mutations of the CaR cause autosomal dominant and sporadic hypoparathyroidism. Affected individuals have hypocalcemia which ranges from mild and asymptomatic to life-threatening. They also show a greater tendency to hypercalciuria than do other patients with hypoparathyroidism. Most, but not all, of the reported activating mutations occur in the amino-terminal, extracellular domain of the receptor. When expressed in cultured cells, mutant receptors can show both increased receptor sensitivity to Ca2+ and increased maximal signal transduction capacity.
钙敏感受体（CaR）是七跨膜结构域G蛋白偶联受体超家族的成员。它在甲状旁腺、肾脏及其他组织中表达。在甲状旁腺中，细胞外钙离子激活CaR会负向调节甲状旁腺激素的分泌。在髓袢升支粗段，受体激活会减少肾脏对钙离子的重吸收。CaR的杂合失活突变会导致家族性良性低钙血症性高钙血症，而纯合失活突变会导致新生儿重症甲状旁腺功能亢进。相反，CaR的激活突变会导致常染色体显性和散发性甲状旁腺功能减退。受影响个体存在低钙血症，程度从轻度无症状到危及生命不等。与其他甲状旁腺功能减退患者相比，他们出现高钙尿症的倾向也更大。已报道的激活突变大多（但并非全部）发生在受体的氨基末端细胞外结构域。当在培养细胞中表达时，突变受体对钙离子的敏感性和最大信号转导能力均会增强。
