title: Peptide YY3-36 and 5-hydroxytryptamine mediate emesis induction by trichothecene deoxynivalenol (vomitoxin).
abstract: Deoxynivalenol (DON, vomitoxin), a trichothecene mycotoxin produced by Fusarium sp. that frequently occurs in cereal grains, has been associated with human and animal food poisoning. Although a common hallmark of DON-induced toxicity is the rapid onset of emesis, the mechanisms for this adverse effect are not fully understood. Recently, our laboratory has demonstrated that the mink (Neovison vison) is a suitable small animal model for investigating trichothecene-induced emesis. The goal of this study was to use this model to determine the roles of two gut satiety hormones, peptide YY3-36 (PYY3-36) and cholecystokinin (CCK), and the neurotransmitter 5-hydroxytryptamine (5-HT) in DON-induced emesis. Following ip exposure to DON at 0.1 and 0.25mg/kg bw, emesis induction ensued within 15-30min and then persisted up to 120min. Plasma DON measurement revealed that this emesis period correlated with the rapid distribution and clearance of the toxin. Significant elevations in both plasma PYY3-36 (30-60min) and 5-HT (60min) but not CCK were observed during emesis. Pretreatment with the neuropeptide Y2 receptor antagonist JNJ-31020028 attenuated DON- and PYY-induced emesis, whereas the CCK1 receptor antagonist devezapide did not alter DON's emetic effects. The 5-HT3 receptor antagonist granisetron completely suppressed induction of vomiting by DON and the 5-HT inducer cisplatin. Granisetron pretreatment also partially blocked PYY3-36-induced emesis, suggesting a potential upstream role for this gut satiety hormone in 5-HT release. Taken together, the results suggest that both PYY3-36 and 5-HT play contributory roles in DON-induced emesis.
authors: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, P.R. China.
authors: Wenda
authors: W
authors: Wu
authors: Melissa A
authors: MA
authors: Bates
authors: Steven J
authors: SJ
authors: Bursian
authors: Brenna
authors: B
authors: Flannery
authors: Hui-Ren
authors: HR
authors: Zhou
authors: Jane E
authors: JE
authors: Link
authors: Haibin
authors: H
authors: Zhang
authors: James J
authors: JJ
authors: Pestka
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D020109:Devazepide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D017829:Granisetron / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008907:Mink; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D019894:Peptide YY / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D012701:Serotonin / Q000097:blood / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D014255:Trichothecenes / Q000097:blood / Q000633:toxicity*; D014839:Vomiting / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism* / Q000517:prevention & control
chemical_list: D000932:Antiemetics; D001549:Benzamides; D002766:Cholecystokinin; D020109:Devazepide; D017829:Granisetron; D010446:Peptide Fragments; D019894:Peptide YY; D010879:Piperazines; D012701:Serotonin; D012702:Serotonin Antagonists; D014255:Trichothecenes; C547250:JNJ-31020028; C061785:peptide YY (3-36); C007262:deoxynivalenol