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首页> 外文期刊>The European Journal of Neuroscience >Dopamine modulates diurnal and circadian rhythms of protein phosphorylation in photoreceptor cells of mouse retina.
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Dopamine modulates diurnal and circadian rhythms of protein phosphorylation in photoreceptor cells of mouse retina.

机译:多巴胺调节小鼠视网膜感光细胞中蛋白质磷酸化的昼夜节律和昼夜节律。

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摘要

Many aspects of photoreceptor metabolism are regulated as diurnal or circadian rhythms. The nature of the signals that drive rhythms in mouse photoreceptors is unknown. Dopamine amacrine cells in mouse retina express core circadian clock genes, leading us to test the hypothesis that dopamine regulates rhythms of protein phosphorylation in photoreceptor cells. To this end we investigated the phosphorylation of phosducin, an abundant photoreceptor-specific phosphoprotein. In mice exposed to a daily light-dark cycle, robust daily rhythms of phosducin phosphorylation and retinal dopamine metabolism were observed. Phospho-phosducin levels were low during the daytime and high at night, and correlated negatively with levels of the dopamine metabolite 3,4-dihydroxyphenylacetic acid. The effect of light on phospho-phosducin levels was mimicked by pharmacological activation of dopamine D4 receptors. The amplitude of the diurnal rhythm of phospho-phosducin was reduced by > 50% in D4 receptor-knockout mice, due tohigher daytime levels of phospho-phosducin. In addition, the daytime level of phospho-phosducin was significantly elevated by L-745,870, a dopamine D4 receptor antagonist. These data indicate that dopamine and other light-dependent processes cooperatively regulate the diurnal rhythm of phosducin phosphorylation. Under conditions of constant darkness a circadian rhythm of phosducin phosphorylation was observed, which correlated negatively with the circadian rhythm of 3,4-dihydroxyphenylacetic acid levels. The circadian fluctuation of phospho-phosducin was completely abolished by constant infusion of L-745,870, indicating that the rhythm of phospho-phosducin level is driven by dopamine. Thus, dopamine release in response to light and circadian clocks drives daily rhythms of protein phosphorylation in photoreceptor cells.
机译:光感受器新陈代谢的许多方面都以昼夜节律或昼夜节律调节。驱动小鼠感光器中节律的信号的性质尚不清楚。小鼠视网膜中的多巴胺无长突细胞表达核心昼夜节律时钟基因,这使我们检验了多巴胺调节感光细胞中蛋白质磷酸化节奏的假设。为此,我们研究了光导蛋白(一种丰富的感光受体特异性磷蛋白)的磷酸化。在暴露于每日明暗周期的小鼠中,观察到了光导蛋白磷酸化和视网膜多巴胺代谢的强劲节律。磷光导素水平在白天较低,在夜间较高,并且与多巴胺代谢产物3,4-二羟基苯基乙酸的含量呈负相关。通过多巴胺D4受体的药理学激活模拟了光对磷光导蛋白水平的影响。由于白天磷水平较高的磷水平,D4受体敲除小鼠的磷水平的昼夜节律幅度降低了50%以上。此外,多巴胺D4受体拮抗剂L-745,870显着提高了白天的磷光诱导素水平。这些数据表明,多巴胺和其他光依赖性过程协同调节光导蛋白磷酸化的昼夜节律。在持续黑暗的条件下,观察到了膦丝素磷酸化的昼夜节律,其与3,4-二羟基苯基乙酸水平的昼夜节律呈负相关。不断输注L-745,870完全消除了磷光导素的昼夜节律波动,表明磷光导素水平的节律是由多巴胺驱动的。因此,响应光和昼夜节律的时钟释放多巴胺会驱动感光细胞中蛋白质磷酸化的日常节律。

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