H2O2 is a novel, endogenous modulator of synaptic dopamine release
H2O2 is a novel, endogenous modulator of synaptic dopamine release
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DOI：
10.1152/jn.2001.85.6.2468
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发表时间：
2001-06-01
影响因子：
2.5
通讯作者：
Rice, ME
中科院分区：
文献类型：
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作者：
Chen, BT;Avshalumov, MV;Rice, ME
最近的证据表明，活性氧（ROS）可能作为神经元过程，包括突触传递的调制器。在这里，我们报告说，突触多巴胺（DA）的释放可以调制的内源性活性氧，过氧化氢。用碳纤维微电极快速扫描循环伏安法监测电刺激豚鼠纹状体脑片DA的释放。外源性H2 O2可逆地抑制诱发释放的存在下，1.5 mM的Ca 2+。然而，外源性H2 O2的有效性被消除或降低的条件，增强Ca 2+的进入，包括增加细胞外Ca 2+浓度（[Ca 2 +]（o）;至2.4 mM），短暂的，高频率的刺激，和抑制性D-2自身受体的阻断。为了测试DA释放是否可以调节内源性H2 O2，释放诱发的H2 O2清除酶，过氧化氢酶的存在下。在过氧化氢酶的存在下，诱发的[DA]（o）比过氧化氢酶洗脱后高60%，表明内源性产生的H2 O2也可以抑制DA释放。重要的是，过氧化氢酶介导作用的Ca 2+依赖性与H2 O2相反：过氧化氢酶在2.4 mM Ca 2+中的增强作用大于1.5 mM，这与较高[Ca 2 +]（o）中H2 O2生成增强一致。总之，这些数据表明，过氧化氢的生产是Ca 2+依赖性的，抑制机制可以饱和，从而防止外源性过氧化氢的进一步影响。这些研究结果首次表明，内源性H2 O2可以调节囊泡神经递质的释放，从而揭示了一个重要的新的信号作用ROS在突触传递。
Recent evidence suggests that reactive oxygen species (ROS) might act as modulators of neuronal processes, including synaptic transmission. Here we report that synaptic dopamine (DA) release can be modulated by an endogenous ROS, H2O2. Electrically stimulated DA release was monitored in guinea pig striatal slices using carbon-fiber microelectrodes with fast-scan cyclic voltammetry. Exogenously applied H2O2 reversibly inhibited evoked release in the presence of 1.5 mM Ca2+. The effectiveness of exogenous H2O2, however, was abolished or decreased by conditions that enhance Ca2+ entry, including increased extracellular Ca2+ concentration ([Ca2+](o); to 2.4 mM), brief, high frequency stimulation, and blockade of inhibitory D-2 autoreceptors. To test whether DA release could be modulated by endogenous H2O2, release was evoked in the presence of the H2O2-scavenging enzyme, catalase. In the presence of catalase, evoked [DA](o) was 60% higher than after catalase washout, demonstrating that endogenously generated H2O2 can also inhibit DA release. Importantly, the Ca2+ dependence of the catalase-mediated effect was opposite to that of H2O2: catalase had a greater enhancing effect in 2.4 mM Ca2+ than in 1.5 mM, consistent with enhanced H2O2 generation in higher [Ca2+](o). Together these data suggest that H2O2 production is Ca2+ dependent and that the inhibitory mechanism can be saturated, thus preventing further effects from exogenous H2O2. These findings show for the first time that endogenous H2O2 can modulate vesicular neurotransmitter release, thus revealing an important new signaling role for ROS in synaptic transmission.