Evidence for cadmium mobilization of intracellular calcium through a divalent cation receptor in renal distal epithelial A6 cells
Evidence for cadmium mobilization of intracellular calcium through a divalent cation receptor in renal distal epithelial A6 cells
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DOI：
10.1007/s00424-002-0912-z
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发表时间：
2002-10-01
影响因子：
4.5
通讯作者：
Bjerregaard, HF
中科院分区：
文献类型：
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作者：
Faurskov, B;Bjerregaard, HF
在负载Fura-2的肾上皮A6细胞中检测Cd 2+对细胞内Ca 2+稳态的影响。Cd 2+（10 μ M ~ 1 mM）以剂量依赖性方式在胞质Ca 2+中产生瞬时峰。磷脂酶C抑制剂U 73122和阳离子受体激动剂新霉素都能减少Cd 2+引起的细胞内Ca 2+增加（[DeltaCa（2+）]（Cd））。此外，毒胡萝卜素，细胞内Ca 2 +-ATP酶的抑制剂，显着降低[DeltaCa（2+）]（镉）。进一步研究表明，当暴露于Cd ~（2+）时，胞内IP 3的静息水平增加了1.45倍。此外，我们发现，Cd 2+相关的重金属，锌和镍，甚至更有效的诱导剂的Ca 2+动员和IP 3的产生比Cd 2+。可以得出结论，Cd 2+，可能Zr 2+和Ni 2+，可以作为激动剂的阳离子敏感受体（CSR）属于G-蛋白受体能够介导IP 3释放的Ca 2+从细胞内存储。A6上皮细胞的CSR受体不能被新霉素或Gd ~（3+）激活，提示该受体不同于钙敏感受体。
The effect of Cd2+ on intracellular Ca2+ homeostasis was examined in renal epithelial A6 cells loaded with Fura-2. Cd2+ (10 muM to I mM) produced a transient spike in cytosolic Ca2+ in a dose-dependent manner. The phospholipase C inhibitor U73122 and the cation receptor agonist, neomycin, both diminish Cd2+- evoked increase in intracellular Ca2+ ([DeltaCa(2+)](Cd)). Further, thapsigargin, an inhibitor of intracellular Ca2+-ATPases, significantly reduced [DeltaCa(2+)](Cd). Extending these observations, inositol-3-phosphate (IP3) binding studies showed that the resting level of intracellular IP3 under-went a 1.45-fold increase when exposed to Cd2+. Furthermore, we found that the Cd2+-related heavy metals, Zn2+ and Ni2+, were even more potent inducers of Ca2+ mobilization and IP3 generation than Cd2+. It can be concluded that Cd2+, and possibly Zr2+ and Ni2+, may act as agonists of a cation-sensing receptor (CSR) belonging to G-protein receptors capable of mediating IP3 release of Ca2+ from intracellular stores. The CSR receptor in A6 epithelia could not be stimulated with neomycin or Gd3+, suggesting that the receptor is different from the calcium-sensing receptor.