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.
These new studies have informed on renal CASR activation thresholds and the downstream CASR-regulated calcium transport mechanisms.
结果:肾脏中CASR的直接激活研究一直很麻烦,并且缺乏有效估计慢性高钙血症或遗传功能获得CASR激活后CASR激活程度的间接测量方法。研究表明,CASR以剂量依赖性方式强烈刺激了孔阻断claudin-14的表达。在高钙血症小鼠中进行肾Casr消融后,这种刺激作用被消除,这表明claudin-14丰度可以衡量肾CASR激活。使用该标记已经导致关于肾CASR激活的意外发现。
结论:这些新研究揭示了肾CASR激活阈值和下游CASR调节的钙转运机制。