Cholecystokinin inhibits endocannabinoid-sensitive hippocampal IPSPs and stimulates others
Cholecystokinin inhibits endocannabinoid-sensitive hippocampal IPSPs and stimulates others
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DOI：
10.1016/j.neuropharm.2007.06.023
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发表时间：
2008-01-01
影响因子：
4.7
通讯作者：
Alger, Bradley E.
中科院分区：
文献类型：
--
作者：
Karson, Miranda A.;Whittington, Kevin C.;Alger, Bradley E.
胆囊收缩素（CCK）是中枢神经系统中最丰富的神经肽。在海马 CA1 区，CCK 与 GABA 共定位于在锥体细胞胞体和顶端树突上突触的中间神经元子集中。含有 CCK 的中间神经元还独特地表达高水平的大麻素受体 CB1，并介导称为 DSI 的逆行信号传导过程。报道的 CCK 对海马抑制性突触后电位 (IPSP) 的影响不一致，包括活性的增加和减少。海马中间神经元非常异质，如果 CCK 以不同的方式影响不同的中间神经元，这些结果可能会得到协调。为了测试这一预测，我们使用了离子型谷氨酸受体被阻断的锥体细胞的尖锐微电极记录，并研究了长期记录期间 CCK 对药理学上不同的 IPSP 组的影响。我们发现 CCK 通过 CCK2 受体发挥作用，增加一些 IPSP 并减少其他 IPSP，最重要的是，受影响的 IPSP 可根据其药理学特性分为两类。卡巴胆碱 (CCh-slPSP) 会增加 IPSP，CCK、omega-芋螺毒素 GVIA 和内源性大麻素则会抑制 IPSP。 CCK (CCK-sIPSP) 增强的 IPSP 会被 omega-agatoxin IVA 阻断，并且不受卡巴胆碱或内源性大麻素的影响。有趣的是，CCK2 拮抗剂可增强 CCh-sIPSP，这表明它们通常可能被内源性 CCK 部分抑制。总之，我们的数据与CCK对源自功能不同的中间神经元的sIPSP具有相反作用的假设相一致。 (c) 2007 Elsevier Ltd. 保留所有权利。
Cholecystokinin (CCK) is the most abundant neuropeptide in the central nervous system. In the hippocampal CA1 region, CCK is co-localized with GABA in a subset of interneurons that synapse on pyramidal cell somata and apical dendrites. CCK-containing interneurons also uniquely express a high level of the cannabinoid receptor, CB1, and mediate the retrograde signaling process called DSI. Reported effects of CCK on inhibitory post-synaptic potentials (IPSPs) in hippocampus are inconsistent, and include both increases and decreases in activity. Hippocampal interneurons are very heterogeneous, and these results could be reconciled if CCK affected different interneurons in different ways. To test this prediction, we used sharp microelectrode recordings from pyramidal cells with ionotropic glutamate receptors blocked, and investigated the effects of CCK on pharmacologically distinct groups of IPSPs during long-term recordings. We find that CCK, acting via the CCK2 receptor, increases some IPSPs and decreases others, and most significantly, that the affected IPSPs can be classified into two groups by their pharmacological properties. IPSPs that are increased by carbachol (CCh-slPSPs), are depressed by CCK, omega-conotoxin GVIA, and endocannabinoids. IPSPs that are enhanced by CCK (CCK-sIPSPs) are blocked by omega-agatoxin IVA, and are unaffected by carbachol or endocannabinoids. Interestingly, a CCK2 antagonist enhances CCh-sIPSPs, suggesting normally they may be partially suppressed by endogenous CCK. In summary, our data are compatible with the hypothesis that CCK has opposite actions on sIPSPs that originate from functionally distinct interneurons. (c) 2007 Elsevier Ltd. All rights reserved.