Calcium-sensing receptor and transient receptor ankyrin-1 mediate emesis induction by deoxynivalenol (vomitoxin)

Wenda Wu, Hui Ren Zhou, Steven J. Bursian, Jane E. Link, James J. Pestka

    Research output: Research - peer-reviewArticle

    • 2 Citations

    Abstract

    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.

    LanguageEnglish (US)
    Pages32-42
    Number of pages11
    JournalToxicological Sciences
    Volume155
    Issue number1
    DOIs
    StatePublished - 2017

    Profile

    Ankyrins
    Calcium-Sensing Receptors
    Vomiting
    deoxynivalenol
    Mink
    Hormones
    Emetics
    Animals
    Enteroendocrine Cells
    Ruthenium Red
    G-Protein-Coupled Receptors
    Food
    N-(2-hydroxy-3-(2-cyano-3-chlorophenoxy)propyl)-1,1-dimethyl-2-(2-nephthyl)ethylamine
    peptide YY (3-36)
    Peptide YY
    Chemical activation
    N-(2-chlorophenylpropyl)-1-(3-methoxyphenyl)ethylamine
    Transient Receptor Potential Channels
    Appetite Depressants
    Mycotoxins

    Keywords

    • 5-HT
    • Calcium-sensing receptor
    • Deoxynivalenol
    • Emesis
    • Mycotoxin
    • Peptide YY3- 36
    • PYY3-36
    • Serotonin
    • Transient receptor potential channel

    ASJC Scopus subject areas

    • Toxicology

    Cite this

    Calcium-sensing receptor and transient receptor ankyrin-1 mediate emesis induction by deoxynivalenol (vomitoxin). / Wu, Wenda; Zhou, Hui Ren; Bursian, Steven J.; Link, Jane E.; Pestka, James J.

    In: Toxicological Sciences, Vol. 155, No. 1, 2017, p. 32-42.

    Research output: Research - peer-reviewArticle

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    abstract = "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.",
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    AU - Bursian,Steven J.

    AU - Link,Jane E.

    AU - Pestka,James J.

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