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The calcium-sensing receptor in physiology and in calcitropic and noncalcitropic diseases.
Nature Reviews Endocrinology ( IF 31.0 ) Pub Date : 2018-12-01 , DOI: 10.1038/s41574-018-0115-0 Fadil M Hannan 1, 2 , Enikö Kallay 3 , Wenhan Chang 4 , Maria Luisa Brandi 5 , Rajesh V Thakker 2
Nature Reviews Endocrinology ( IF 31.0 ) Pub Date : 2018-12-01 , DOI: 10.1038/s41574-018-0115-0 Fadil M Hannan 1, 2 , Enikö Kallay 3 , Wenhan Chang 4 , Maria Luisa Brandi 5 , Rajesh V Thakker 2
Affiliation
The Ca2+-sensing receptor (CaSR) is a dimeric family C G protein-coupled receptor that is expressed in calcitropic tissues such as the parathyroid glands and the kidneys and signals via G proteins and β-arrestin. The CaSR has a pivotal role in bone and mineral metabolism, as it regulates parathyroid hormone secretion, urinary Ca2+ excretion, skeletal development and lactation. The importance of the CaSR for these calcitropic processes is highlighted by loss-of-function and gain-of-function CaSR mutations that cause familial hypocalciuric hypercalcaemia and autosomal dominant hypocalcaemia, respectively, and also by the fact that alterations in parathyroid CaSR expression contribute to the pathogenesis of primary and secondary hyperparathyroidism. Moreover, the CaSR is an established therapeutic target for hyperparathyroid disorders. The CaSR is also expressed in organs not involved in Ca2+ homeostasis: it has noncalcitropic roles in lung and neuronal development, vascular tone, gastrointestinal nutrient sensing, wound healing and secretion of insulin and enteroendocrine hormones. Furthermore, the abnormal expression or function of the CaSR is implicated in cardiovascular and neurological diseases, as well as in asthma, and the CaSR is reported to protect against colorectal cancer and neuroblastoma but increase the malignant potential of prostate and breast cancers.
中文翻译:
生理学以及嗜钙性和非嗜钙性疾病中的钙敏感受体。
Ca2+ 感应受体 (CaSR) 是一种二聚体家族 C G 蛋白偶联受体,在促钙组织(如甲状旁腺和肾脏)中表达,并通过 G 蛋白和 β-arrestin 发出信号。CaSR 在骨骼和矿物质代谢中起着关键作用,因为它调节甲状旁腺激素分泌、尿 Ca2+ 排泄、骨骼发育和泌乳。CaSR 对这些嗜钙过程的重要性表现为功能丧失和功能获得性 CaSR 突变分别导致家族性低尿钙性高钙血症和常染色体显性遗传性低钙血症,以及甲状旁腺 CaSR 表达的改变导致原发性和继发性甲状旁腺功能亢进症的发病机制。此外,CaSR 是甲状旁腺功能亢进性疾病的既定治疗靶点。CaSR 也在不参与 Ca2 + 稳态的器官中表达:它在肺和神经元发育、血管张力、胃肠道营养感应、伤口愈合以及胰岛素和肠内分泌激素的分泌中具有非促钙作用。此外,CaSR 的异常表达或功能与心血管和神经系统疾病以及哮喘有关,据报道 CaSR 可以预防结直肠癌和神经母细胞瘤,但会增加前列腺癌和乳腺癌的恶性潜力。
更新日期:2019-01-26
中文翻译:
生理学以及嗜钙性和非嗜钙性疾病中的钙敏感受体。
Ca2+ 感应受体 (CaSR) 是一种二聚体家族 C G 蛋白偶联受体,在促钙组织(如甲状旁腺和肾脏)中表达,并通过 G 蛋白和 β-arrestin 发出信号。CaSR 在骨骼和矿物质代谢中起着关键作用,因为它调节甲状旁腺激素分泌、尿 Ca2+ 排泄、骨骼发育和泌乳。CaSR 对这些嗜钙过程的重要性表现为功能丧失和功能获得性 CaSR 突变分别导致家族性低尿钙性高钙血症和常染色体显性遗传性低钙血症,以及甲状旁腺 CaSR 表达的改变导致原发性和继发性甲状旁腺功能亢进症的发病机制。此外,CaSR 是甲状旁腺功能亢进性疾病的既定治疗靶点。CaSR 也在不参与 Ca2 + 稳态的器官中表达:它在肺和神经元发育、血管张力、胃肠道营养感应、伤口愈合以及胰岛素和肠内分泌激素的分泌中具有非促钙作用。此外,CaSR 的异常表达或功能与心血管和神经系统疾病以及哮喘有关,据报道 CaSR 可以预防结直肠癌和神经母细胞瘤,但会增加前列腺癌和乳腺癌的恶性潜力。