Phosphatidylinositol-linked novel D1 dopamine receptor facilitates long-term depression in rat hippocampal CA1 synapses
Phosphatidylinositol-linked novel D1 dopamine receptor facilitates long-term depression in rat hippocampal CA1 synapses
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DOI：
10.1016/j.neuropharm.2009.05.001
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发表时间：
2009-08-01
影响因子：
4.7
通讯作者：
Chen, Jian-Guo
中科院分区：
文献类型：
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作者：
Liu, Jue;Wang, Wei;Chen, Jian-Guo
最近的研究表明，磷脂酰肌醇(PI)连接的D-1多巴胺受体选择性激动剂SKF83959通过激活大脑中的磷脂酶C来介导磷脂酰肌醇的水解。SKF83959在突触可塑性中的具体作用尚未得到很好的阐明。本研究的目的是研究SKF83959在大鼠海马片CA1区长期抑郁(LTD)中的作用，并探讨导致这些变化的分子事件。结果表明，刺激SKF83959可剂量依赖性地显著压低场兴奋性突触后电位(FEPSP)，并促进LFS诱发LTD。SKF83959-Enabled Ltd需要激活磷脂酶C(PLC)。NMDA受体参与了这一反应。钙离子螯合剂BAPTA-AM可阻止SKF83959促进的LTD，表明细胞内游离钙浓度([Ca~(2+)](I))升高可能是这种反应的原因。此外，在钙调神经磷酸酶(PP2B)抑制剂环孢素A(CsA)存在的情况下，SKF83959促进的LTD被显著抑制，并与钙调神经磷酸酶A的表达持续增加有关。综上所述，这些发现表明PI连接的D，多巴胺受体在海马LTD的神经调节中发挥了新的作用。(C)2009爱思唯尔有限公司。保留所有权利。
Recent work has demonstrated that a phosphatidylinositol (PI)-linked D-1 dopamine receptor selective agonist, SKF83959, mediates phosphatidylinositol hydrolysis via activation of phospholipase C in brain. Specific contributions of SKF83959 to synaptic plasticity have not been well elucidated. The aim of the current investigation was to characterize the role of SKF83959 on long-term depression (LTD) in the CA1 region of rat hippocampal slices and to explore the molecular events leading to these changes. The results indicated that SKF83959 stimulation significantly depressed field excitatory postsynaptic potentials (fEPSPs) in a dose-dependent manner and facilitated the induction of LTD by LFS. SKF83959-facilitated LTD required activation of phospholipase C (PLC). NMDA receptors were involved in this response. Calcium chelator, BAPTA-AM prevented SKF83959-facilitated LTD, indicating that cytosolic free calcium concentration ([Ca2+](i)) elevation could account for this response. Furthermore, SKF83959-facilitated LTD was significantly depressed in the presence of calcineurin (PP2B) inhibitors cyclosporin A (CsA) and associated with a persistent increase in the expression of calcineurin A. Taken together, these findings demonstrate a novel role for PI-linked D, dopamine receptor in the neuromodulation of hippocampal LTD. (C) 2009 Elsevier Ltd. All rights reserved.