New insights into renal calcium-sensing receptor activation.

IF 2.2 3区医学 Q3 PERIPHERAL VASCULAR DISEASE

Current Opinion in Nephrology and Hypertension Pub Date : 2024-07-01 Epub Date: 2024-05-01 DOI:10.1097/MNH.0000000000000998

Henrik Dimke

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引用次数: 0

Abstract

Purpose of review: Activation of the calcium-sensing receptor (CASR) in the parathyroid gland suppresses the release of parathyroid hormone (PTH). Furthermore, activation of the renal CASR directly increases the urinary excretion of calcium, by inhibiting transepithelial calcium transport in the nephron. Gain-of-function mutations in the CASR gene lead to autosomal dominant hypocalcemia 1 (ADH1), with inappropriately low PTH levels and hypocalcemia, indicative of excessive activation of the parathyroid CASR. However, hypercalciuria is not always observed. The reason why the manifestation of hypercalciuria is not uniform among ADH1 patients is not well understood.

Recent findings: Direct activation of the CASR in the kidney has been cumbersome to study, and an indirect measure to effectively estimate the degree of CASR activation following chronic hypercalcemia or genetic gain-of-function CASR activation has been lacking. Studies have shown that expression of the pore-blocking claudin-14 is strongly stimulated by the CASR in a dose-dependent manner. This stimulatory effect is abolished after renal Casr ablation in hypercalcemic mice, suggesting that claudin-14 abundance may gauge renal CASR activation. Using this marker has led to unexpected discoveries regarding renal CASR activation.

Summary: These new studies have informed on renal CASR activation thresholds and the downstream CASR-regulated calcium transport mechanisms.

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肾脏钙传感受体激活的新发现

综述的目的：激活甲状旁腺的钙传感受体（CASR）可抑制甲状旁腺激素（PTH）的释放。此外，肾脏 CASR 的激活可抑制肾小球内钙的跨上皮转运，从而直接增加钙的尿排泄。CASR 基因的功能增益突变会导致常染色体显性低钙血症 1（ADH1），出现不适当的低 PTH 水平和低钙血症，表明甲状旁腺 CASR 被过度激活。然而，并非总能观察到高钙尿症。ADH1患者高钙尿症表现不一致的原因尚不十分清楚：肾脏中 CASR 的直接激活一直是研究的难点，而且一直缺乏一种间接测量方法来有效估计慢性高钙血症或基因功能增益 CASR 激活后 CASR 的激活程度。研究表明，CASR 会以剂量依赖的方式强烈刺激孔阻断因子 claudin-14 的表达。高钙血症小鼠的肾Casr消融后，这种刺激作用消失，这表明Claudin-14的丰度可以衡量肾CASR的激活情况。总结：这些新研究为肾CASR激活阈值和CASR调控的下游钙转运机制提供了信息。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Opinion in Nephrology and Hypertension 医学-泌尿学与肾脏学

CiteScore

5.70

自引率

6.20%

发文量

132

审稿时长

6-12 weeks

期刊介绍： A reader-friendly resource, Current Opinion in Nephrology and Hypertension provides an up-to-date account of the most important advances in the field of nephrology and hypertension. Each issue contains either two or three sections delivering a diverse and comprehensive coverage of all the key issues, including pathophysiology of hypertension, circulation and hemodynamics, and clinical nephrology. Current Opinion in Nephrology and Hypertension is an indispensable journal for the busy clinician, researcher or student.