Activation of phosphatidylinositol-linked D1-like receptors increases spontaneous glutamate release in rat somatosensory cortical neurons in vitro
Activation of phosphatidylinositol-linked D1-like receptors increases spontaneous glutamate release in rat somatosensory cortical neurons in vitro
复制标题
体外，磷脂酰肌醇连接的 D1 样受体的激活可增加大鼠体感皮层神经元的自发谷氨酸释放
DOI：
10.1016/j.brainres.2010.04.043
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发表时间：
2010-07-09
期刊：
影响因子：
2.9
通讯作者：
Zhen, Xuechu
中科院分区：
文献类型：
--
作者：
Chu, Hong-Yuan;Yang, Zhi;Zhen, Xuechu
中枢多巴胺能系统主要通过D-1受体/cAMP/PKA通路对脑内各区域自发性谷氨酸释放进行调节。目前尚不清楚磷脂酰肌醇（PI）连接的D-1样受体是否也参与这种调节作用。取代的苯基苯并氮杂卓SKF 83959作为非典型D-1样受体的选择性激动剂的鉴定推动了研究它们对脑中自发谷氨酸释放的影响。在本研究中，SKF 83959对自发兴奋性突触后电流（sEPSC）的影响进行了研究，通过全细胞记录从V-VI层锥体神经元在大鼠体感皮层切片。SKF 83959（10-100 μ M）灌注显著增加sEPSC的频率，而对sEPSC的振幅没有显著影响。D-1样受体拮抗剂SCH 23390可阻断SKF 83959对sEPSC频率的增加，而D-2受体拮抗剂、α 1肾上腺素受体拮抗剂和5-HT 2A/2C受体拮抗剂则不能阻断SKF 83959对sEPSC频率的增加。PLC β抑制剂U-73122、IP 3受体拮抗剂2-APB、PKC抑制剂chelerythrine chloride和TRPV 1拮抗剂capsazepine可阻断SKF 83959的作用，而PKA抑制剂H-89和腺苷酸环化酶激活剂forskolin则无此作用。总之，在D-1受体/PLC β信号通路激活后，PKC对TRPV 1通道的敏化介导了SKF 83959诱导的sEPSC频率增加。据我们所知，这是第一个药理学证据，表明PI连接的D-1样多巴胺受体确实存在于皮质神经元的突触前末梢中，并在控制自发谷氨酸释放方面发挥重要作用。(C)2010 Elsevier B. V.保留所有权利。
Central dopaminergic system exerts profound modulation on spontaneous glutamate release in various brain regions mainly through D-1 receptor/cAMP/PKA pathway. It remains unclear whether the phosphatidylinositol (PI)-linked D-1-like receptors are also involved in such modulatory actions. The identification of substituted phenylbenzazepine SKF83959 as the selective agonist for the atypical D-1-like receptors has given impetus to study their influence on the spontaneous glutamate release in the brain. In the present study the effects of SKF83959 on the spontaneous excitatory postsynaptic currents (sEPSCs) were investigated through whole-cell recording from layer V-VI pyramidal neurons in rat somatosensory cortical slices. Perfusion with SKF83959 (10-100 mu M) considerably increased the frequency of sEPSCs, while had no significant effect on the amplitude of sEPSCs. The increase of sEPSC frequency by SKF83959 was blocked by SCH23390, a D-1-like receptor antagonist, but not by the antagonists for D-2 receptor, alpha(1)-adrenoceptor and 5-HT2A/2C receptor. U-73122 (PLC beta inhibitor), 2-APB (IP3 receptor antagonist), chelerythrine chloride (PKC inhibitor) and capsazepine (TRPV1 antagonist) could block the effects of SKF83959, whereas H-89 (PKA inhibitor) and forskolin (adenylyl cyclase activator) had no effect. Taken together, sensitization of TRPV1 channels by PKC after activation of D-1 receptor/PLC beta signaling pathway mediated SKF83959-induced increase in the sEPSC frequency. To our knowledge, this is the first pharmacological evidence that PI-linked D-1-like dopamine receptors do exist in presynaptic terminals of cortical neurons and play an important role in controlling the spontaneous glutamate release. (C) 2010 Elsevier B.V. All rights reserved.