Regulation of type 1 IP3 receptor expression by dopamine D2-like receptors via AP-1 and NFATc4 activation
Regulation of type 1 IP3 receptor expression by dopamine D2-like receptors via AP-1 and NFATc4 activation
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多巴胺 D2 样受体通过 AP-1 和 NFATc4 激活调节 1 型 IP3 受体表达
DOI：
10.1016/j.neuropharm.2013.03.036
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发表时间：
2013
影响因子：
4.7
通讯作者：
S. Ohkuma
中科院分区：
文献类型：
--
作者：
K. Mizuno;K. Kurokawa;S. Ohkuma
I型肌醇1，4，5-三磷酸受体(IP3Rs-1)和兰尼定受体是调节细胞内钙离子浓度的主要钙通道。虽然我们最近的报道证实了刺激多巴胺D1样和D2R样受体诱导的IP3R-1上调在心理依赖中的重要作用，但D2R对IP3R-1表达的确切调控机制尚未阐明。用与D2Rs偶联的钙相关信号转导通路的抑制剂处理小鼠大脑皮层神经元，分析转录因子调控IP3R-1表达的机制。选择性D2R激动剂奎比罗可上调IP3R-1蛋白的表达，并可被Gβγ调节剂Gallein、磷脂酶C抑制剂U73122、细胞内钙离子螯合剂BAPTA-AM、钙调素抑制剂W7、钙调素依赖的蛋白激酶抑制剂KN-93和钙调神经磷酸酶抑制剂FK506显著抑制。免疫细胞化学检测显示，喹比罗可增加CFos和磷酸化cJun在细胞核内的表达，并促进NFATc4复合体从胞浆向细胞核的移位。此外，喹比罗还直接在AP-1和IP3R-1启动子区域以及NFATc4和IP3R-1启动子区域之间招募结合。这些结果表明，D2Rs在G-βγ激活后通过增加AP-1和NFATC4与IP3R-1启动子区域的结合而促进IP3R-1基因的转录。
Type 1 inositol 1,4,5-trisphosphate receptors (IP3Rs-1), together with ryanodine receptors, are major calcium channels to regulate intracellular Ca2+concentration. Although our recent report demonstrates the essential involvement of IP3R-1 up-regulation induced by dopamine D1-like and D2-like receptor (D1 and D2R) stimulation in psychological dependence, exact regulatory mechanisms of IP3R-1 expression by D2Rs have not yet been clarified. Mouse cerebral cortical neurons were treated with inhibitor of Ca2+-related signal transduction pathways coupling to D2Rs and used to analyze the mechanisms of IP3R-1 expression regulated by transcriptional factor. A selective D2R agonist, quinpirole, up-regulated IP3R-1 protein following its mRNA increase, which was significantly inhibited by gallein (a Gβγ modulator), U73122 (a phospholipase C inhibitor), BAPTA-AM (an intracellular calcium chelating reagent), W7 (a calmodulin inhibitor), KN-93 (a calmodulin-dependent protein kinases inhibitor), and FK506 (a calcineurin inhibitor). Immunocytochemical assessment showed that quinpirole increased expression of both cFos and phosphorylated-cJun in nucleus and enhanced translocation of NFATc4 complex to nucleus from cytoplasm. In addition, quinpirole directly recruited bindings between AP-1 and IP3R-1 promoter region and between NFATc4 and IP3R-1 promoter region. These results indicate that D2Rs enhance IP3R-1 gene transcription via increased bindings of AP-1 and NFATc4 to IP3R-1 promoter region after Gβγ activation.
影响因子：
4.4
作者：
F. Lobo;R. Zanjani;N. Ho;T. Chatila;R. Fuleihan
通讯作者：
F. Lobo;R. Zanjani;N. Ho;T. Chatila;R. Fuleihan
DOI：
10.1073/pnas.93.20.10803
发表时间：
1996-10-01
影响因子：
11.1
作者：
Enslen, H;Tokumitsu, H;Soderling, TR
通讯作者：
Soderling, TR