Thapsigargin stimulates intracellular calcium mobilization and inhibits parathyroid hormone release.
Thapsigargin stimulates intracellular calcium mobilization and inhibits parathyroid hormone release.
复制标题
毒胡萝卜素刺激细胞内钙动员并抑制甲状旁腺激素释放。
DOI：
10.1002/jbmr.5650100511
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Lattyak,B
中科院分区：
文献类型：
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作者：
Shoback,D;Chen,TH;Pratt,S;Lattyak,B
Ca2+and other divalent cations like Sr2+, Ba2+, and Mg2+stimulate rapid and sustained increases in intracellular Ca2+([Ca2+]i) and 1,4,5‐inositol trisphosphate (1,4,5‐InsP3) presumably by interacting with recently identified parathyroid cell membrane Ca2+receptors. We used thapsigargin (THAPS), an inhibitor of the microsomal Ca2+‐ATPase, to deplete InsP3‐sensitive intracellular Ca2+stores to determine whether sustained increases in [Ca2+]idue to divalent cations require intact cytosolic Ca2+pools. In Fura 2‐loaded parathyroid cells, THAPS produced a gradual increase in [Ca2+]iwhich reached a steady‐state level by 2–3 minutes. The effect of THAPS (3 × 10−6M) was substantial with [Ca2+]i, rising from 281 ± 27 nM at 0.5 mM Ca2+to a peak value of 684 ± 30 nM (p< 0.0001). The addition of Sr2+to cells at 0.5 mM extracellular Ca2+induced an immediate 2‐to 3‐fold increase in [Ca2+]iwhich stabilized at a [Ca2+]iabove baseline for ≥10 minutes. THAPS (3 × 10−6M) pretreatment for ≥5 minutes blocked this sustained‐phase increment in [Ca2+]idue to Sr2+. In the absence of extracellular Ca2+, there was a slight but nonsignificant effect of THAPS on [Ca2+]i. Incubation of cells with THAPS did not change the levels of3H‐inositol phosphates (InsP3, InsP2, and InsP1) or alter Sr2+‐induced accumulation of InsP3, InsP2, and InsP1. THAPS substantially reduced parathyroid hormone secretion at 1.0 mM Ca2+by 20 ± 16, 57 ± 8, 75 ± 10, and 83 ± 9% at 10−7, 3 × 10−7, 10−6, and 3 × 10−6M THAPS, respectively. We conclude that depletion of intracellular Ca2+stores by THAPS stimulates Ca2+mobilization, presumably from extracellular sources, and that this agent and divalent cations such as Sr2+activate the same pathway for sustained Ca2+mobilization. The inhibition of secretion by THAPS supports the idea that increases in [Ca2+]iplay a suppressive role in the control of hormone release in the parathyroid.
