中文摘要：食品中常见的霉菌毒素脱氧雪腐镰刀菌烯醇（DON，呕吐毒素）能引起人和动物拒食和呕吐，给健康带来不利。肠道内分泌细胞（EECs）分泌激素，介导DON引起厌食及催吐作用。先前利用克隆的EEC模型，本实验室发现了DON诱导激活钙敏感受体（CaSR）（一种G蛋白偶联受体（GPCR））及瞬时受体锚蛋白1(TRPA1)（一种瞬时受体电位（TRP）通道），驱动Ca2+介导的激素分泌。与这些体外研究结果一致，CaSR和TRPA1介导DON诱导小鼠（不能呕吐的动物模型）的饱腹激素释放及拒食行为。然而，这种GPCR和TRP对DON催吐的作用仍不清楚。为了弄清这个问题，我们检验了DON通过激活CaSR和TRPA1引发水貂呕吐的假设。本研究有力地证实了CaSR和TRPA1的激活对DON诱导的呕吐起着关键作用。
外文摘要：The common foodborne mycotoxin deoxynivalenol (DON, vomitoxin) can negatively impact animal and human health by causing food refusal and vomiting. Gut enteroendocrine cells (EECs) secrete hormones that mediate DON’s anorectic and emetic effects. In prior work utilizing a cloned EEC model, our laboratory discovered that DON-induced activation of calcium-sensing receptor (CaSR), a G-coupled protein receptor (GPCR), and transient receptor ankyrin-1 (TRPA1), a transient receptor potential (TRP) channel, drives Ca2+-mediated hormone secretion. Consistent with these in vitro findings, CaSR and TRPA1 mediate DON-induced satiety hormone release and food refusal in the mouse, an animal model incapable of vomiting. However, the roles of this GPCR and TRP in DON’s emetic effects remain to be determined. To address this, we tested the hypothesis that DON triggers emesis in mink by activating CaSR and TRPA1. Oral gavage with selective agonists for CaSR (R-568) or TRPA1 (allyl isothiocyanate; AITC) rapidly elicited emesis in the mink in dose-dependent fashion. Oral pretreatment of the animals with the CaSR antagonist NPS-2143 or the TRP antagonist ruthenium red (RR), respectively, inhibited these responses. Importantly, DON-induced emesis in mink was similarly inhibited by oral pretreatment with NPS-2143 or RR. In addition, these antagonists suppressed concurrent DON-induced elevations in plasma peptide YY3-36 and 5-hydroxytryptamine—hormones previously demonstrated to mediate the toxin’s emetic effects in mink. Furthermore, antagonist co-treatment additively suppressed DON-induced emesis and peptide YY 3-36 release. To summarize, the observations here strongly suggest that activation of CaSR and TRPA1 might have critical roles in DON-induced emesis.
外文关键词：mycotoxin；deoxynivalenol；calcium-sensing receptor；transient receptor potential channel；emesis；peptide YY3-36；PYY3-36；serotonin；5-HT
作者：Wu, WD；Zhou, HR；Bursian, SJ；Link, JE；Pestka, JJ
作者单位：Nanjing Agr Univ
期刊名称：TOXICOLOGICAL SCIENCES
期刊影响因子：3.88
出版年份：2017
出版刊次：1
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