Staphylococcal enterotoxin induces emesis through increasing serotonin release in intestine and it is downregulated by cannabinoid receptor 1
Staphylococcal enterotoxin induces emesis through increasing serotonin release in intestine and it is downregulated by cannabinoid receptor 1
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DOI：
10.1111/j.1462-5822.2007.00957.x
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发表时间：
2007-09-01
影响因子：
3.4
通讯作者：
Nakane, Akio
中科院分区：
文献类型：
--
作者：
Hu, Dong-Liang;Zhu, Gang;Nakane, Akio
由金黄色葡萄球菌产生的葡萄球菌肠毒素(SES)是世界上最常见的引起人类食物中毒的细菌超抗原性毒素。然而，目前还不清楚SES如何诱导呕吐及其呕吐信号通路。我们使用一种小的呕吐动物模型--家麝鼠--来研究海洋诱导呕吐的机制。5-羟色胺(5-HT)合成抑制剂和5-HT3受体拮抗剂可抑制SEA引起的动物呕吐。SEA可增加小肠5-羟色胺的释放。5，7-二羟色胺(5，7-DHT)可明显抑制SEA引起的呕吐。SEA引起的呕吐也通过手术迷走神经切断术消除。此外，大麻素(CB)受体激动剂可抑制SEA引起的呕吐，该作用可被CB1拮抗剂逆转。5-羟色胺释放和CB1受体在肠粘膜神经丛和肌间神经丛均有表达。此外，CB1受体激动剂显著减少肠道5-羟色胺的释放。这些结果表明，SEA可引起肠道而不是脑内5-羟色胺的释放，迷走神经传入神经元上的5-HT3受体在SEA引起的呕吐中起重要作用。此外，CB系统通过减少肠道中5-羟色胺的释放来下调SEA引起的呕吐。
Staphylococcal enterotoxins (SEs) produced by Staphylococcus aureus are the most recognizable bacterial superantigenic toxins causing food poisoning in humans throughout the world. However, it remains unclear how SEs induce emesis and its emetic signal pathway. We investigated a mechanism of SEA-induced emesis using a small emetic animal model, house musk shrew. SEA-induced emesis in the animals was inhibited by a 5-hydroxytryptamine (5-HT) synthesis inhibitor and a 5-HT3 receptor antagonist. SEA could increase 5-HT release in the small intestine. Pre-treatment with 5,7-dihydroxytryptamine (5,7-DHT) markedly inhibited SEA-induced emesis. SEA-induced emesis was also abolished by surgical vagotomy. Furthermore, cannabinoid (CB) receptor agonists inhibited SEA-induced emesis, and the action was reversed by a CB1 antagonist. Both 5-HT release and CB1 receptor expression were found in the mucosal and myenteric plexus of the intestine. Moreover, a CB1 receptor agonist significantly decreased the 5-HT release in the intestine. These results demonstrate that SEA induces 5-HT release in intestine, rather than in brain, and that the 5-HT3 receptors on vagal afferent neurons are essential for SEA-stimulated emesis. In addition, SEA-induced emesis is downregulated by the CB system through decreasing 5-HT release in intestine.