Etelcalcetide decreases the PTH?calcium setpoint without changing maximum and minimum PTH secretion in mice with primary hyperparathyroidism
Etelcalcetide decreases the PTH?calcium setpoint without changing maximum and minimum PTH secretion in mice with primary hyperparathyroidism
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Etelcalcetide 降低原发性甲状旁腺功能亢进症小鼠 PTH 钙设定点而不改变最大和最小 PTH 分泌
DOI：
10.1007/s00774-020-01169-z
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发表时间：
2021
影响因子：
3.3
通讯作者：
Emoto Masanori
中科院分区：
文献类型：
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作者：
Hayashi Noriyuki;Imanishi Yasuo;Hirakawa Tomoe;Kobayashi Ikue;Tateishi Tomomi;Miyaoka Daichi;Nagata Yuki;Mori Katsuhito;Morioka Tomoaki;Inoue Atsuto;Harada Kazutsune;Inaba Masaaki;Emoto Masanori
IntroductionEtelcalcetide结合到钙敏感受体（CaSR）的细胞外结构域，而西那卡塞结合到CaSR的7-跨膜结构域;然而，它是未知的，Etelcalcetide是否具有类似的影响西那卡塞对甲状旁腺激素（PTH）secretory.Materials和方法PTH-钙设定点和最大和最小PTH分泌使用“体内设定点分析”确定。在原发性甲状旁腺功能亢进（PC）和野生型（WT）小鼠模型中获得PTH-钙设定点，PC小鼠分为两组。Etelcalcetide（3.0 mg/kg BW/天）或溶剂通过渗透泵给药7天后获得设定点。交叉给药7天后，再次获得设定点。交叉给药后获取甲状旁腺，通过免疫组织化学分析CaSR表达。结果Etelcalcetide给药使设定点从9.03 ± 0.56 mg/dL显着降低至6.80 ± 0.28 mg/dL，给予溶剂后恢复至8.81 ± 0.38 mg/dL。在第二组小鼠中，溶剂给药并未改变设定点（8.84 ± 0.69 mg/dL至8.98 ± 0.63 mg/dL），但随后的etelcalcetide给药将其显着降低至7.10 ± 0.72 mg/dL。最大和最小PTH分泌量无显著变化。甲状旁腺钙调素受体的表达水平较低，在PC小鼠比在WT小鼠，但是，没有显着差异，观察两个小鼠groups.ConclusionEtelcalcetide之间的PTH-钙的设定点，而不改变最大和最小的PTH分泌PC小鼠，这表明，像西那卡塞，etelcalcetide具有拟钙的效力。
IntroductionEtelcalcetide binds to the extracellular domain of the calcium-sensing receptor (CaSR), while cinacalcet binds to the 7-transmembrane domain of the CaSR; however, it is unknown, whether etelcalcetide has similar effects to cinacalcet on parathyroid hormone (PTH) secretion.Materials and methodsThe PTH–calcium setpoint and maximum and minimum PTH secretion were determined using an ‘in vivo setpoint analyses.’ The PTH–calcium setpoint was obtained in a mouse model of primary hyperparathyroidism (PC) and wild-type (WT) mice, with PC mice divided into two groups. The setpoint was obtained after 7 days of etelcalcetide (3.0 mg/kg BW/day) or vehicle administration via anosmotic pump. After 7 days of crossover administration, the setpoint was obtained again. Parathyroid glands were obtained after crossover administration, and CaSR expression was analyzed by immunohistochemistry.ResultsEtelcalcetide administration significantly decreased the setpoint from 9.03 ± 0.56 mg/dL to 6.80 ± 0.28 mg/dL, which was restored to 8.81 ± 0.38 mg/dL after vehicle administration. In the second group of mice, vehicle administration did not alter the setpoint (8.84 ± 0.69 mg/dL to 8.98 ± 0.63 mg/dL), but subsequent etelcalcetide administration significantly decreased it to 7.10 ± 0.72 mg/dL. There was no significant change in maximum and minimum PTH secretion. Expression levels of parathyroid CaSR were lower in PC mice than in WT mice; however, no significant differences were observed between the two mouse groups.ConclusionEtelcalcetide decreased the PTH–calcium setpoint without changing maximum and minimum PTH secretion in PC mice, suggesting that like cinacalcet, etelcalcetide has calcimimetic potency.