Shi Yanyan, Jia Yinjun, Zhang Wei
School of Life Sciences, State Key Laboratory of Membrane Biology, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing 100084, China.
Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
Sci Adv. 2025 Sep 12;11(37):eadv1143. doi: 10.1126/sciadv.adv1143.
Vomiting is a common yet poorly understood symptom, largely due to the lack of conventional animal models. This study establishes a model for vomiting triggered by berberine ingestion. Our findings reveal that this response is mediated by the chemoreceptor TrpA1, which is indirectly activated by berberine via the mAChRs-PLC pathway. Berberine induces acetylcholine release from foregut epithelial cells, which triggers tachykinin secretion from intestinal tracheal cells. Tachykinins contract the visceral muscles, particularly the P4 pump of the foregut, and suppress myosuppressin release from pars intercerebralis neurons, thereby promoting crop motility. We further demonstrate the conservation of key genes involved in mammalian vomiting regulation. Overall, this study provides a molecular and cellular framework for understanding vomiting and introduces as a genetic model for mechanistic studies.
呕吐是一种常见但却了解甚少的症状,这主要是由于缺乏传统的动物模型。本研究建立了一个由摄入小檗碱引发呕吐的模型。我们的研究结果表明,这种反应是由化学感受器TrpA1介导的,小檗碱通过毒蕈碱型乙酰胆碱受体-磷脂酶C途径间接激活TrpA1。小檗碱诱导前肠上皮细胞释放乙酰胆碱,从而触发肠道气管细胞分泌速激肽。速激肽使内脏肌肉收缩,特别是前肠的P4泵,并抑制脑间部神经元释放肌抑制素,从而促进嗉囊运动。我们进一步证明了参与哺乳动物呕吐调节的关键基因的保守性。总体而言,本研究为理解呕吐提供了一个分子和细胞框架,并引入了一个用于机制研究的遗传模型。