中文摘要：单端孢霉烯毒素脱氧雪腐镰刀菌烯醇（DON，呕吐毒素）能抑制摄食量并损害生长从而影响人畜健康。DON诱导小鼠胃肠道内分泌细胞(EECs)分泌异常饱腹感激素，引起厌食反应。最近体外研究小鼠STC-1 EEC模型将DON诱导的分泌饱腹感激素与钙敏感受体（CaSR），一种G蛋白偶联受体，及瞬时受体电位锚蛋白(TRPA1)，一种TRP通道的激活结合起来。然而，类似的机制是否在体内介导DON厌食反应仍不清楚。为此，本研究假设DON诱导小鼠拒食及饱腹感激素的释放与CaSR和TRPA1的激活相关并进行了测试。研究发现，这些体内研究数据与之前的体外研究结果一样，都支持DON通过诱导EEC分泌饱足感激素，活化CaSR和TRPA1引发拒食的论点。
外文摘要：Food contamination by the trichothecene mycotoxin deoxynivalenol (DON, vomitoxin) has the potential to adversely affect animal and human health by suppressing food intake and impairing growth. In mice, the DON-induced anorectic response results from aberrant satiety hormone secretion by enteroendocrine cells (EECs) of the gastrointestinal tract. Recent in vitro studies in the murine STC-1 EEC model have linked DON-induced satiety hormone secretion to activation of calcium-sensing receptor (CaSR), a G-coupled protein receptor, and transient receptor potential ankyrin-1 (TRPA1), a TRP channel. However, it is unknown whether similar mechanisms mediate DON’s anorectic effects in vivo. Here, we tested the hypothesis that DON-induced food refusal and satiety hormone release in the mouse are linked to activation of CaSR and TRPA1. Oral treatment with selective agonists for CaSR (R-568) or TRPA1 (allyl isothiocyanate (AITC)) suppressed food intake in mice, and the agonist’s effects were suppressed by pretreatment with corresponding antagonists NPS-2143 or ruthenium red (RR), respectively. Importantly, NPS-2143 or RR inhibited both DON-induced food refusal and plasma elevations of the satiety hormones cholecystokinin (CCK) and peptide YY3–36 (PYY3–36); cotreatment with both antagonists additively suppressed both anorectic and hormone responses to DON. Taken together, these in vivo data along with prior in vitro findings support the contention that activation of CaSR and TRPA1 contributes to DON-induced food refusal by mediating satiety hormone exocytosis from EEC.
外文关键词：Mycotoxin；Deoxynivalenol；Calcium-sensing receptor；Transient receptor potential channel；Anorexia；Cholecystokinin；CCK；Peptide YY3-36；PYY3-36
作者：Wu, WD；Zhou, HR；Pestka, JJ
作者单位：Nanjing Agr Univ
期刊名称：ARCHIVES OF TOXICOLOGY
期刊影响因子：6.637
出版年份：2017
出版刊次：1
点击下载：钙敏感受体（CaSR）和瞬时受体电位锚蛋白-1（TRPA1）在脱氧雪腐镰刀菌烯醇（呕吐毒素）引起小鼠厌食反应中的作用