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首页> 外文期刊>The European Journal of Neuroscience >Bidirectional regulation of dopamine D2 and neurotensin NTS1 receptors in dopamine neurons.
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Bidirectional regulation of dopamine D2 and neurotensin NTS1 receptors in dopamine neurons.

机译：多巴胺神经元中多巴胺D2和神经降压素NTS1受体的双向调节。

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Several lines of evidence suggest a close association between dopamine (DA) and neurotensin (NT) systems in the CNS. Indeed, in the rodent brain, abundant NT-containing fibres are found in DA-rich areas such as the ventral tegmental area and substantia nigra. Moreover, it has been shown in vivo that NT, acting through its high-affinity receptor (NTS1), reduces the physiological and behavioural effects of DA D2 receptor (D2R) activation, a critical autoreceptor feedback system regulating DA neurotransmission. However, the mechanism of this interaction is still elusive. The aim of our study was thus to reproduce in vitro the interaction between D2R and NTS1, and then to characterize the mechanisms implicated. We used a primary culture model of DA neurons prepared from transgenic mice expressing green fluorescent protein under the control of the tyrosine hydroxylase promoter. In these cultures, DA neurons endogenously express both D2R and NTS1. Using electrophysiological recordings, we show that activation of D2R directly inhibits the firing rate of DA neurons. In addition, we find that NT, acting through a NTS1-like receptor, is able to reduce D2R autoreceptor function independently of its ability to enhance DA neuron firing, and that this interaction occurs through a protein kinase C- and Ca(2+)-dependent mechanism. Furthermore, prior activation of D2R reduces the ability of NTS1 to induce intracellular Ca(2+) mobilization. Our findings provide evidence for bidirectional interaction between D2R and NTS1 in DA neurons, a regulatory mechanism that could play a key role in the control of the activity of these neurons.
机译：有几条证据表明，中枢神经系统中的多巴胺（DA）与神经降压素（NT）系统密切相关。实际上，在啮齿动物的大脑中，在富含DA的区域（如腹侧被盖区和黑质）中发现了大量的含NT纤维。此外，体内已显示NT通过其高亲和力受体（NTS1）起作用，可降低DA D2受体（D2R）激活（调节DA神经传递的关键自体受体反馈系统）的生理和行为影响。但是，这种相互作用的机制仍然难以捉摸。因此，我们的研究目的是在体外重现D2R和NTS1之间的相互作用，然后表征所涉及的机制。我们使用从表达酪氨酸羟化酶启动子控制下的绿色荧光蛋白的转基因小鼠制备的DA神经元的主要培养模型。在这些文化中，DA神经元内源性表达D2R和NTS1。使用电生理记录，我们表明D2R的激活直接抑制DA神经元的放电率。此外，我们发现NT通过像NTS1样受体起作用，能够降低D2R自身受体功能，而与增强DA神经元放电的能力无关，并且这种相互作用是通过蛋白激酶C-和Ca（2+）发生的依赖机制。此外，D2R的先前激活降低了NTS1诱导细胞内Ca（2+）动员的能力。我们的发现为DA神经元中D2R和NTS1之间的双向相互作用提供了证据，这是一种调控机制，可在这些神经元的活动控制中发挥关键作用。

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