title: Deoxynivalenol (Vomitoxin)-Induced Cholecystokinin and Glucagon-Like Peptide-1 Release in the STC-1 Enteroendocrine Cell Model Is Mediated by Calcium-Sensing Receptor and Transient Receptor Potential Ankyrin-1 Channel.
abstract: Food refusal is a hallmark of exposure of experimental animals to the trichothecene mycotoxin deoxynivalenol (DON), a common foodborne contaminant. Although studies in the mouse suggest that DON suppresses food intake by aberrantly inducing the release of satiety hormones from enteroendocrine cells (EECs) found in the gut epithelium, the underlying mechanisms for this effect are not understood. To address this gap, we employed the murine neuroendocrine tumor STC-1 cell line, a widely used EEC model, to test the hypothesis that DON-induced hormone exocytosis is mediated by G protein-coupled receptor (GPCR)-mediated Ca(2+) signaling. The results indicate for the first time that DON elicits Ca(2)-dependent secretion of cholecystokinin (CCK) and glucagon-like peptide-1(7-36) amide (GLP-1), hormones that regulate food intake and energy homeostasis and that are products of 2 critical EEC populations--I cells of the small intestine and L cells of the large intestine, respectively. Furthermore, these effects were mediated by the GPCR Ca(2+)-sensing receptor (CaSR) and involved the following serial events: (1)PLC-mediated activation of the IP3 receptor and mobilization of intracellular Ca(2+) stores, (2) activation of transient receptor potential melastatin-5 ion channel and resultant L-type voltage-sensitive Ca(2+) channel-facilitated extracellular Ca(2+) entry, (3) amplification of extracellular Ca(2+) entry by transient receptor potential ankyrin-1 channel activation, and finally (4) Ca(2+)-driven CCK and GLP-1 excytosis. These in vitro findings provide a foundation for future investigation of mechanisms by which DON and other trichothecenes modulate EEC function in ex vivo and in vivo models.
authors: *Department of Food Science and Human Nutrition, Department of Microbiology and Molecular Genetics and Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824.
authors: Hui-Ren
authors: HR
authors: Zhou
authors: *Department of Food Science and Human Nutrition, Department of Microbiology and Molecular Genetics and Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824 *Department of Food Science and Human Nutrition, Department of Microbiology and Molecular Genetics and Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824 *Department of Food Science and Human Nutrition, Department of Microbiology and Molecular Genetics and Center for Integrative Toxicology, Michigan State University, East Lansing, Michigan 48824 pestka@msu.edu.
authors: James J
authors: JJ
authors: Pestka
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D045744:Cell Line, Tumor; D002766:Cholecystokinin / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019858:Enteroendocrine Cells / Q000187:drug effects* / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D005506:Food Contamination; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D051379:Mice; D034622:RNA Interference; D044169:Receptors, Calcium-Sensing; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D050051:Transient Receptor Potential Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014255:Trichothecenes / Q000633:toxicity*; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: C577923:CASR protein, mouse; D020746:Calcium Channels, L-Type; D053496:Inositol 1,4,5-Trisphosphate Receptors; D044169:Receptors, Calcium-Sensing; D043562:Receptors, G-Protein-Coupled; D000074025:TRPA1 Cation Channel; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels; D014255:Trichothecenes; C475685:Trpa1 protein, mouse; C498617:Trpm5 protein, mouse; D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin; D010738:Type C Phospholipases; C007262:deoxynivalenol
keywords: CCK; CaSR; GLP-1; TRPA1; deoxynivalenol; mycotoxin