The T-2 toxin, a major secondary metabolite of Fusarium Gramineae, is considered a great risk to humans and animals due to its toxicity, such as inducing emesis. The mechanism of emesis is a complex signal involving an imbalance of hormones and neurotransmitters, as well as activity of visceral afferent neurons. The T-2 toxin has been proven to induce emesis and possess the capacity to elevate expressions of intestinal hormones glucagon-like peptide-17-36 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), both of which are important emetic factors. In addition, the activation of calcium-sensitive receptor (CaSR) and transient receptor potential (TRP) channels are engaged in intestinal hormone release. However, it is unknown whether hormones GLP-1 and GIP mediate T-2 toxin-induced emetic response through activating CaSR and TRP channels. To further assess the mechanism of T-2 toxin-induced emesis, we studied the hypothesis that T-2 toxin-caused emetic response and intestinal hormones GLP-1 and GIP released in mink are associated with activating calcium transduction. Following oral gavage and intraperitoneal injection T-2 toxin, emetic responses were observed in a dose-dependent manner, which notably corresponded to the secretion of GLP-1 and GIP, and were suppressed by pretreatment with respective antagonist Exending9-39 and Pro3GIP. Additional research found that NPS-2143 (NPS) and ruthenium red (RR), respective antagonists of CaSR and TRP channels, dramatically inhibited both T-2 toxin-induced emesis response and the expression of plasma GLP-1 and GIP. According to these data, we observed that T-2 toxin-induced emetic response corresponds to secretion of GLP-1 and GIP via calcium transduction.

• Keywords
• T-2 toxin, brain–gut peptide, calcium-sensing receptor, emesis, transient receptor potential channel,
• MeSH
• Amides MeSH
• Emetics MeSH
• Glucagon-Like Peptide 1 metabolism   MeSH
• Glucose pharmacology   MeSH
• Insulin MeSH
• Peptide Fragments pharmacology   MeSH
• Receptors, G-Protein-Coupled MeSH
• T-2 Toxin * toxicity   MeSH
• Calcium MeSH
• Gastric Inhibitory Polypeptide metabolism   pharmacology   MeSH
• Animals MeSH
• Vomiting MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Amides MeSH
• Emetics MeSH
• Glucagon-Like Peptide 1 MeSH
• Glucose MeSH
• Insulin MeSH
• Peptide Fragments MeSH
• Receptors, G-Protein-Coupled MeSH
• T-2 Toxin * MeSH
• Calcium MeSH
• Gastric Inhibitory Polypeptide MeSH

Deoxynivalenol (DON), the most naturally-occurring trichothecenes, may affect animal and human health by causing vomiting as a hallmark of food poisoning. Deoxynivalenol-3-glucoside (D3G) usually co-occurs with DON as its glucosylated form and is another emerging food safety issue in recent years. However, the toxicity of D3G is not fully understood compared to DON, especially in emetic potency. The goals of this research were to (1) compare emetic effects to D3G by oral and intraperitoneal (IP) routes and relate emetic effects to brain-gut peptides glucose-dependent insulinotropic polypeptide (GIP) and substance P (SP) in mink; (2) determine the roles of calcium-sensing receptor (CaSR) and transient receptor potential (TRP) channel in D3G's emetic effect. Both oral and IP exposure to D3G elicited marked emetic events. This emetic response corresponded to an elevation of GIP and SP. Blocking the GIP receptor (GIPR) diminished emetic response induction by GIP and D3G. The neurokinin 1 receptor (NK-1R) inhibitor Emend® restrained the induction of emesis by SP and D3G. Importantly, CaSR antagonist NPS-2143 or TRP channel antagonist ruthenium red dose-dependently inhibited both D3G-induced emesis and brain-gut peptides GIP and SP release; cotreatment with both antagonists additively suppressed both emetic and brain-gut peptide responses to D3G. To summarize, our findings demonstrate that activation of CaSR and TRP channels contributes to D3G-induced emesis by mediating brain-gut peptide exocytosis in mink.

• Keywords
• brain-gut peptide, calcium-sensing receptor, deoxynivalenol-3-glucoside, emesis, transient receptor potential channel,
• MeSH
• Emetics * toxicity   MeSH
• Glucose MeSH
• Glucosides MeSH
• Mink MeSH
• Receptors, Gastrointestinal Hormone MeSH
• Receptors, G-Protein-Coupled MeSH
• Substance P MeSH
• Trichothecenes * chemistry   toxicity   MeSH
• Animals MeSH
• Vomiting chemically induced   MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• deoxynivalenol-3-glucoside MeSH Browser
• Emetics * MeSH
• gastric inhibitory polypeptide receptor MeSH Browser
• Glucose MeSH
• Glucosides MeSH
• Receptors, Gastrointestinal Hormone MeSH
• Receptors, G-Protein-Coupled MeSH
• Substance P MeSH
• Trichothecenes * MeSH