Vasoactive intestinal polypeptide requires parallel changes in adenylate cyclase and phospholipase C to entrain circadian rhythms to a predictable phase
Vasoactive intestinal polypeptide requires parallel changes in adenylate cyclase and phospholipase C to entrain circadian rhythms to a predictable phase
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DOI：
10.1152/jn.00966.2010
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发表时间：
2011-05-01
影响因子：
2.5
通讯作者：
Herzog, Erik D.
中科院分区：
文献类型：
--
作者：
An, Sungwon;Irwin, Robert P.;Herzog, Erik D.
An S，欧文RP，艾伦CN，Tsai C，Herzog ED.血管活性肠多肽需要腺苷酸环化酶和磷脂酶C的平行变化来将昼夜节律带入可预测的阶段。J Neurophysiol 105：2289-2296，2011.首次发表于2011年3月9日; doi：10.1152/jn.00966.2010。视交叉上核（SCN）中的昼夜节律振荡依赖于单个细胞内周期（PER）1和PER 2蛋白的转录抑制以及细胞之间的血管活性肠多肽（VIP）信号传导。由于VIP由SCN神经元以昼夜节律模式释放，并且在光刺激后，已经表明其在与环境光周期的同步中发挥作用。然而，VIP是否或如何影响昼夜节律基因表达或行为尚不清楚。在这里，我们测试了VIP介导的SCN节律夹带所需的候选信号通路。我们发现，VIP的单次应用以与光不同的时间和剂量依赖性方式重置PER 2节律。不像VIP介导的信号在其他类型的细胞，腺苷酸环化酶和磷脂酶C活性的同时拮抗作用，需要阻断VIP诱导的SCN节律的相移。与此一致，VIP迅速增加大多数SCN神经元的细胞内cAMP。重要的是，每日VIP治疗在几天内将PER 2节律带入预测的相位角，这取决于VIP的浓度和VIP应用之间的间隔。我们的结论是，VIP通过腺苷酸环化酶和磷脂酶C活性的快速和平行的变化，诱导SCN神经元之间的昼夜节律。
An S, Irwin RP, Allen CN, Tsai C, Herzog ED. Vasoactive intestinal polypeptide requires parallel changes in adenylate cyclase and phospholipase C to entrain circadian rhythms to a predictable phase. J Neurophysiol 105: 2289-2296, 2011. First published March 9, 2011; doi:10.1152/jn.00966.2010.-Circadian oscillations in the suprachiasmatic nucleus (SCN) depend on transcriptional repression by Period (PER) 1 and PER2 proteins within single cells and on vasoactive intestinal polypeptide (VIP) signaling between cells. Because VIP is released by SCN neurons in a circadian pattern, and, after photic stimulation, it has been suggested to play a role in the synchronization to environmental light cycles. It is not known, however, if or how VIP entrains circadian gene expression or behavior. Here, we tested candidate signaling pathways required for VIP-mediated entrainment of SCN rhythms. We found that single applications of VIP reset PER2 rhythms in a time-and dose-dependent manner that differed from light. Unlike VIP-mediated signaling in other cell types, simultaneous antagonism of adenylate cyclase and phospholipase C activities was required to block the VIP-induced phase shifts of SCN rhythms. Consistent with this, VIP rapidly increased intracellular cAMP in most SCN neurons. Critically, daily VIP treatment entrained PER2 rhythms to a predicted phase angle within several days, depending on the concentration of VIP and the interval between VIP applications. We conclude that VIP entrains circadian timing among SCN neurons through rapid and parallel changes in adenylate cyclase and phospholipase C activities.