Gymnopilins, a product of a hallucinogenic mushroom, inhibit the nicotinic acetylcholine receptor
Gymnopilins, a product of a hallucinogenic mushroom, inhibit the nicotinic acetylcholine receptor
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DOI：
10.1016/j.toxicon.2014.01.014
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发表时间：
2014-04-01
期刊：
影响因子：
2.8
通讯作者：
Aimi, Tadanori
中科院分区：
文献类型：
--
作者：
Kayano, Tomohiko;Kitamura, Naoki;Aimi, Tadanori
Gymnopilins是在致幻蘑菇Gymnopilus junonius的子实体中产生的物质。尽管目前关于裸毛素对动物组织的生物学效应的报道较少，但人们认为裸毛素是G. junonius中毒本研究发现裸毛素对乙酰胆碱诱发的神经元细胞PC 12细胞反应有抑制作用，并探讨了其作用机制。从野生裸壳菌Gymnopilins的子实体中分离纯化得到裸壳素。junonius在日本收集的。Ca ~（2+）显像显示裸毛素使ACh诱发的[Ca ~（2+）]（i）升高幅度降低约50%，并消除了阿托品存在下剩余的ACh反应。Gymnopilins可显著降低烟碱ACh受体激动剂DMPP和尼古丁引起的[Ca ~（2+）]（i）升高幅度。在全细胞电压钳记录中，裸毛素抑制DMPP诱发的电流，但不影响电压门控Ca 2+通道电流。这些结果表明裸毛素直接作用于烟碱型ACh受体并抑制其活性。这种生物学作用可能是引起G. junonius中毒(C)2014爱思唯尔有限公司版权所有。
Gymnopilins are substances produced in fruiting bodies of the hallucinogenic mushroom, Gymnopilus junonius. Although, only a few biological effects of gymnopilins on animal tissues have been reported, it is believed that gymnopilins are a key factor of the G. junonius poisoning. In the present study, we found that gymnopilins inhibited ACh-evoked responses in neuronal cell line, PC12 cell, and determine the underlying mechanism. Gymnopilins were purified from wild fruiting bodies of G. junonius collected in Japan. Ca2+-imaging revealed that gymnopilins reduced the amplitude of ACh-evoked [Ca2+](i) rises by about 50% and abolished the ACh responses remaining in the presence of atropine. Gymnopilins greatly reduced the amplitude of [Ca2+](i) rises evoked by nicotinic ACh receptor agonists, 1,1-Dimethy1-4-phenylpiperazinium iodide (DMPP) and nicotine. In the whole-cell voltage clamp recording, gymnopilins inhibited the DMPP-evoked currents, but did not affect the voltage-gated Ca2+ channel currents. These results indicate that gymnopilins directly act on nicotinic ACh receptors and inhibit their activity. This biological action of gymnopilins may be one of the causes of the G. junonius poisoning. (C) 2014 Elsevier Ltd. All rights reserved.