Faurskov Brian, Bjerregaard Henning F
Novozymes A/S, Kalundborg, Denmark.
Pflugers Arch. 2002 Oct;445(1):40-50. doi: 10.1007/s00424-002-0912-z. Epub 2002 Sep 6.
The effect of Cd(2+) on intracellular Ca(2+) homeostasis was examined in renal epithelial A6 cells loaded with Fura-2. Cd(2+) (10 microM to 1 mM) produced a transient spike in cytosolic Ca(2+) in a dose-dependent manner. The phospholipase C inhibitor U73122 and the cation receptor agonist, neomycin, both diminish Cd(2+)-evoked increase in intracellular Ca(2+) (deltaCa(2+)). Further, thapsigargin, an inhibitor of intracellular Ca(2+)-ATPases, significantly reduced deltaCa(2+). Extending these observations, inositol-3-phosphate (IP(3)) binding studies showed that the resting level of intracellular IP(3) underwent a 1.45-fold increase when exposed to Cd(2+). Furthermore, we found that the Cd(2+)-related heavy metals, Zn(2+) and Ni(2+), were even more potent inducers of Ca(2+) mobilization and IP(3) generation than Cd(2+). It can be concluded that Cd(2+), and possibly Zn(2+) and Ni(2+), may act as agonists of a cation-sensing receptor (CSR) belonging to G-protein receptors capable of mediating IP(3) release of Ca(2+) from intracellular stores. The CSR receptor in A6 epithelia could not be stimulated with neomycin or Gd(3+), suggesting that the receptor is different from the calcium-sensing receptor.
在装载了Fura-2的肾上皮A6细胞中检测了Cd(2+)对细胞内Ca(2+)稳态的影响。Cd(2+)（10微摩尔至1毫摩尔）以剂量依赖的方式在细胞质Ca(2+)中产生短暂峰值。磷脂酶C抑制剂U73122和阳离子受体激动剂新霉素均减少了Cd(2+)诱发的细胞内Ca(2+)增加（δCa(2+)）。此外，细胞内Ca(2+)-ATP酶抑制剂毒胡萝卜素显著降低了δCa(2+)。进一步扩展这些观察结果，肌醇-3-磷酸（IP(3)）结合研究表明，当暴露于Cd(2+)时，细胞内IP(3)的静息水平增加了1.45倍。此外，我们发现与Cd(2+)相关的重金属Zn(2+)和Ni(2+)在诱导Ca(2+)动员和IP(3)生成方面比Cd(2+)更有效。可以得出结论，Cd(2+)，可能还有Zn(2+)和Ni(2+)，可能作为属于G蛋白受体的阳离子感应受体（CSR）的激动剂，能够介导从细胞内储存中释放Ca(2+)的IP(3)。新霉素或Gd(3+)不能刺激A6上皮细胞中的CSR受体，这表明该受体与钙感应受体不同。
