Zwart R, De Filippi G, Broad L M, McPhie G I, Pearson K H, Baldwinson T, Sher E
Eli Lilly and Company Limited, Lilly Research Centre, Erl Wood Manor, Sunninghill Road, Surrey GU20 6PH, Windlesham, UK.
Neuropharmacology. 2002 Sep;43(3):374-84. doi: 10.1016/s0028-3908(02)00094-1.
The effects of 5-hydroxyindole (5-HI) have been investigated on human alpha 7 nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes and GH4 cells, on native alpha 7 nAChRs expressed by IMR-32 cells and on alpha 7 nAChR-mediated events in mossy fibre-granule cell synapses in rat cerebellar slices. In oocytes expressing alpha 7 nAChRs, 5-HI potentiated sub-maximal, 60 micro M ACh-induced ion currents in a concentration-dependent manner, the threshold effective concentration being 30 micro M. 5-HI itself did not act as an agonist on alpha 7 nAChRs. A maximum potentiation of 12 times the control was observed at 20 mM 5-HI. The effect of 1 mM 5-HI on the concentration-response curve for ACh revealed that 5-HI increased the potency as well as the efficacy of ACh on alpha 7 nAChRs. 5-HI also potentiated alpha 7-mediated increases in intracellular free calcium levels in both mammalian cells heterologously expressing human alpha 7 nAChRs and in human IMR-32 neuroblastoma cells expressing native alpha 7 nAChRs. At mossy fibre-granule cell synapses, application of 1 mM ACh induced glutamate-evoked excitatory post-synaptic currents (EPSCs). Co-application of 1 mM 5-HI with 1 mM ACh further increased the frequency of the EPSCs. The ACh-induced release, as well as the 5-HI-induced enhancement of release, were blocked by 1-10 nM methyllycaconitine or 200 nM alpha-bungarotoxin, demonstrating that both effects were mediated by presynaptic alpha 7 nAChRs. The results demonstrate that responses mediated by alpha 7 nAChRs are strongly potentiated by 5-HI.
研究了5-羟色胺（5-HI）对非洲爪蟾卵母细胞和GH4细胞中表达的人α7烟碱型乙酰胆碱受体（nAChRs）、IMR-32细胞表达的天然α7 nAChRs以及大鼠小脑切片苔藓纤维-颗粒细胞突触中α7 nAChR介导的事件的影响。在表达α7 nAChRs的卵母细胞中，5-HI以浓度依赖的方式增强亚最大浓度（60 μM）乙酰胆碱（ACh）诱导的离子电流，阈值有效浓度为30 μM。5-HI本身对α7 nAChRs不起激动剂作用。在20 mM 5-HI时观察到最大增强倍数为对照的12倍。1 mM 5-HI对ACh浓度-反应曲线的影响表明，5-HI增加了ACh对α7 nAChRs的效力和效能。5-HI还增强了在异源表达人α7 nAChRs的哺乳动物细胞和表达天然α7 nAChRs的人IMR-32神经母细胞瘤细胞中α7介导的细胞内游离钙水平的升高。在苔藓纤维-颗粒细胞突触处，施加1 mM ACh可诱导谷氨酸诱发的兴奋性突触后电流（EPSCs）。1 mM 5-HI与1 mM ACh共同施加进一步增加了EPSCs的频率。ACh诱导的释放以及5-HI诱导的释放增强均被1-10 nM甲基lycaconitine或200 nMα-银环蛇毒素阻断，表明这两种效应均由突触前α7 nAChRs介导。结果表明，α7 nAChRs介导的反应被5-HI强烈增强。
