Nongenomic mechanism of glucocorticoid inhibition of bradykinin-induced calcium influx in PC12 cells: possible involvement of protein kinase C.
Nongenomic mechanism of glucocorticoid inhibition of bradykinin-induced calcium influx in PC12 cells: possible involvement of protein kinase C.
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DOI：
10.1016/s0024-3205(03)00168-1
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发表时间：
2003-04
期刊：
影响因子：
6.1
通讯作者：
J. Qiu;Chengcheng Wang;Xiu-ying Huang;Yi-Zhang Chen
中科院分区：
文献类型：
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作者：
J. Qiu;Chengcheng Wang;Xiu-ying Huang;Yi-Zhang Chen
许多兴奋剂，包括缓激肽 (BK)，可以诱导 PC12 细胞中 [Ca2+]i 的增加。缓激肽通过 G 蛋白转导，但不通过电压敏感钙通道，通过细胞内 Ca2+ 释放和细胞外 Ca2+ 流入，诱导 [Ca2+]i 增加。在本实验中，我们分析了皮质酮（Cort）如何影响BK诱导的细胞内Ca2+释放和细胞外Ca2+内流，并进一步研究了糖皮质激素的作用机制。为了分离 BK 诱导的细胞内 Ca2+ 释放和细胞外 Ca2+ 内流，使用无 Ca2+/Ca2+- 重新引入方案。结果如下：(1)Cort能快速抑制BK诱导的Ca2+内流，但对细胞内Ca2+释放影响不明显。 (2)Cort-BSA(BSA-conjugate Cort)对BK诱导的Ca2+内流的抑制作用与游离Cort的作用相同。 (3)蛋白激酶C(PKC)激活剂(佛波醇12-肉豆蔻酸酯13-乙酸酯)可以模拟Cort的抑制作用，PKC抑制剂Gö6976可以逆转Cort的抑制作用。 (4)百日咳毒素预处理时，Cort对BK诱导的Ca2+内流没有抑制作用。结果首次表明，Cort 可能通过假定的膜受体发挥作用，并通过百日咳毒素敏感的 G 蛋白-PKC 途径抑制 BK 诱导的 Ca2+ 内流。
Many stimulants, including bradykinin (BK), can induce increase in [Ca2+]iin PC12 cells. Bradykinin induces an increase in [Ca2+]ivia intracellular Ca2+release and extracellular Ca2+influx through the transduction of G protein, but not through voltage-sensitive calcium channels. In this experiment, We analyzed how corticosterone (Cort) influences BK-induced intracellular Ca2+release and extracellular Ca2+influx, and further studied the mechanism of glucocorticoid's action. To dissociate the intracellular Ca2+release and extracellular Ca2+influx induced by BK, the Ca2+-free/Ca2+- reintroduction protocol was used. The results were as follows: (1) The Ca2+influx induced by BK could be rapidly inhibited by Cort, but intracellular Ca2+release could not be affected significantly. (2) The inhibitory effect of Cort-BSA (BSA -conjugated Cort) on Ca2+influx induced by BK was the same as the effect of free Cort. (3) Protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate) could mimic and PKC inhibitor Gö6976 could reverse the inhibitory effect of Cort. (4) There was no inhibitory effect of Cort on Ca2+influx induced by BK when pretreated with pertussis toxin. The results suggested, for the first time, that Cort might act via a putative membrane receptor and inhibit the Ca2+influx induced by BK through the pertussis toxin -sensitive G protein-PKC pathway.