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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Inhibitory effect of nitric oxide on dopamine transporters: interneuronal communication without receptors.
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Inhibitory effect of nitric oxide on dopamine transporters: interneuronal communication without receptors.

机译：一氧化氮对多巴胺转运蛋白的抑制作用：无受体的神经元间通讯。

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Previously we observed that Nomega-nitro-L-arginine methyl ester (l-NAME) decreased the striatal dopamine (DA) release in microdialysis experiments and this effect was completely diminished in the presence of the DA uptake inhibitor nomifensine, indicating that the effect was mediated via the DA transporter. The aim of the present work was to study the direct effect of nitrergic compounds on DA uptake. We measured the uptake of [3H]DA in striatal slices and found that the nitric oxide (NO) generator sodium nitroprussid (100 microM) decreased the uptake by 66%. In contrast, the NO synthase inhibitor L-NAME (100 microM) increased the DA uptake by 80%, while the inactive D-NAME had no effect on uptake. Our data indicate that NO exerts an inhibitory effect on DA transporters. Since the production of NO by neuronal NO synthase is closely related to the activation of NMDA receptors, the level of NO around synapses reflects the activity of glutamatergic neurotransmission. The strength of excitatory input, therefore, can be nonsynaptically signaled by NO to the surrounding dopaminergic neurons via the inhibitory tone on transporters. The concomitant elevation of DA concentration around the activated synapse represents the response of dopaminergic system, which can adapt to the changing excitatory activity without receiving glutamatergic input and without expressing glutamate receptors. Thus, the effect of NO on transporters represents a new form of interneuronal communication, a nonsynaptic interaction without receptors.
机译：先前我们观察到，在微透析实验中，Nomega-硝基-L-精氨酸甲酯（l-NAME）降低了纹状体多巴胺（DA）的释放，并且在存在DA吸收抑制剂nomifensine的情况下，这种作用完全减弱了，表明该作用是通过DA转运蛋白介导。本工作的目的是研究硝化化合物对DA吸收的直接作用。我们测量了纹状体切片中[3H] DA的吸收，发现一氧化氮（NO）产生剂硝普钠（100 microM）使吸收减少了66％。相反，NO合酶抑制剂L-NAME（100 microM）使DA摄取增加了80％，而无活性的D-NAME对摄取没有影响。我们的数据表明，NO对DA转运蛋白具有抑制作用。由于神经元一氧化氮合酶产生一氧化氮与NMDA受体的激活密切相关，因此突触周围一氧化氮的水平反映了谷氨酸能神经传递的活性。因此，兴奋性输入的强度可以通过转运蛋白上的抑制音通过非突触传递给周围的多巴胺能神经元。活化突触周围DA浓度的同时升高代表了多巴胺能系统的反应，该系统可以适应不断变化的兴奋性活动，而无需接受谷氨酸能输入且不表达谷氨酸受体。因此，NO对转运蛋白的影响代表了一种新形式的神经元间通讯，即没有受体的非突触相互作用。

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