8-Nitro-cGMP modulates exocytosis in adrenal chromaffin cells
8-Nitro-cGMP modulates exocytosis in adrenal chromaffin cells
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8-硝基-cGMP 调节肾上腺嗜铬细胞的胞吐作用
DOI：
10.1016/j.bbrc.2020.03.045
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发表时间：
2020
影响因子：
3.1
通讯作者：
Ihara Hideshi
中科院分区：
文献类型：
--
作者：
Tsutsuki Hiroyasu;Kasamatsu Shingo;Kunieda Kohei;Ida Tomoaki;Sawa Tomohiro;Sasakawa Nobuyuki;Akaike Takaaki;Ihara Hideshi
一氧化氮(NO)介导的环鸟苷3‘，5’-单磷酸(CGMP)的产生是控制多种神经功能的重要信号通路，包括胞吐递质的释放。8-硝基-cGMP是一种新型的cGMP硝化衍生物，它不仅能激活cGMP依赖的蛋白激酶(PKG)，而且具有膜通透性和氧化还原活性，从而产生超氧化物和鸟苷化蛋白。到目前为止，还没有研究涉及8-硝基-cGMP对胞吐动力学的影响。在此，我们旨在评估8-硝基-cGMP对牛嗜铬细胞去极化诱导儿茶酚胺释放的调节作用。8-硝基-cGMP在依赖NO供体的牛嗜铬细胞中产生。安培分析表明，8-硝基-cGMP调制了嗜铬细胞分泌峰的动力学参数，特别是降低了单个峰的速度，导致电流峰高、斜率β和斜率γ绝对值减小。这种调节作用不依赖于PKG信号和超氧阴离子的产生。这是第一个证明8-硝基-cGMP调节胞吐作用的研究，并提供了对胞吐作用新的调节机制的见解。
Nitric oxide (NO)-mediated production of cyclic guanosine 3′,5′-monophosphate (cGMP) is a crucial signaling pathway that controls a wide array of neuronal functions, including exocytotic neurotransmitter release. A novel nitrated derivative of cGMP, 8-nitro-cGMP, not only activates cGMP-dependent protein kinase (PKG), but also has membrane permeability and redox activity to produce superoxide andS-guanylated protein. To date, no studies have addressed the effects of 8-nitro-cGMP on exocytotic kinetics. Here, we aimed to assess the 8-nitro-cGMP-mediated modulation of the depolarization-evoked catecholamine release from bovine chromaffin cells. 8-Nitro-cGMP was produced in bovine chromaffin cells dependent on NO donor. Amperometric analysis revealed that 8-nitro-cGMP modulated the kinetic parameters of secretory spikes from chromaffin cells, particularly decreased the speed of individual spikes, resulting in a reduced amperometric spike height, slope β, and absolute value of slope γ. The modulatory effects were independent of the PKG signal and superoxide production. This is the first study to demonstrate that 8-nitro-cGMP modulates exocytosis and provide insights into a novel regulatory mechanism of exocytosis.