CHIMERIC NICOTINIC SEROTONERGIC RECEPTOR COMBINES DISTINCT LIGAND-BINDING AND CHANNEL SPECIFICITIES
CHIMERIC NICOTINIC SEROTONERGIC RECEPTOR COMBINES DISTINCT LIGAND-BINDING AND CHANNEL SPECIFICITIES
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DOI：
10.1038/366479a0
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发表时间：
1993-12-02
期刊：
影响因子：
64.8
通讯作者：
BERTRAND, D
中科院分区：
文献类型：
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作者：
EISELE, JL;BERTRAND, S;BERTRAND, D
神经元烟碱α 7（nAChR）和5-羟色胺（5 HT 3）受体1 -3是具有同源拓扑结构的配体门控离子通道，具有共同的激活和脱敏反应。然而，这些同源寡聚受体不同的药理学的结合位点的激动剂和竞争性antagonists 3，4，并在其敏感性Ca 2+离子。α 7通道对Ca 2+离子具有高度渗透性5，6，外部Ca 2+离子以变构方式增强对乙酰胆碱的渗透性反应，如其他神经元nAChRs 7，8所示。相比之下，5 HT 3通道对Ca 2+离子不可渗透，但被它们阻断3，9。为了将这些特性分配给一级结构的限定结构域，我们构建了几种重组嵌合体α 7 - 5 HT 3受体。我们在这里报告的结构之一，表达的功能受体，其中包含钙离子通道仍然被阻断，但被激活的烟碱配体和增强的外部钙离子。
THE neuronal nicotinic alpha7 (nAChR) and 5-hydroxytryptamine (5HT3) receptors1-3 are ligand-gated ion channels with a homologous topological organization and have activation and desensitization reactions in common. Yet these homo-oligomeric receptors differ in the pharmacology of their binding sites for agonists and competitive antagonists3,4, and in their sensitivity to Ca2+ ions. The alpha7 channel is highly permeable to Ca2+ ions5,6 and external Ca2+ ions potentiate, in an allosteric manner, the permeability response to acetylcholine, as shown for other neuronal nAChRs7,8. The 5HT3 channel, in contrast, is not permeable to Ca2+ ions, but blocked by them3,9. To assign these properties to delimited domains of the primary structure, we constructed several recombinant chimaeric alpha7-5HT3 receptors. We report here that one of the constructs expresses a functional receptor that contains the serotonergic channel still blocked by Ca2+ ions, but is activated by nicotinic ligands and potentiated by external Ca2+ ions.