title: Potential roles for calcium-sensing receptor (CaSR) and transient receptor potential ankyrin-1 (TRPA1) in murine anorectic response to deoxynivalenol (vomitoxin).
abstract: Food contamination by the trichothecene mycotoxin deoxynivalenol (DON, vomitoxin) has the potential to adversely affect animal and human health by suppressing food intake and impairing growth. In mice, the DON-induced anorectic response results from aberrant satiety hormone secretion by enteroendocrine cells (EECs) of the gastrointestinal tract. Recent in vitro studies in the murine STC-1 EEC model have linked DON-induced satiety hormone secretion to activation of calcium-sensing receptor (CaSR), a G-coupled protein receptor, and transient receptor potential ankyrin-1 (TRPA1), a TRP channel. However, it is unknown whether similar mechanisms mediate DON's anorectic effects in vivo. Here, we tested the hypothesis that DON-induced food refusal and satiety hormone release in the mouse are linked to activation of CaSR and TRPA1. Oral treatment with selective agonists for CaSR (R-568) or TRPA1 (allyl isothiocyanate (AITC)) suppressed food intake in mice, and the agonist's effects were suppressed by pretreatment with corresponding antagonists NPS-2143 or ruthenium red (RR), respectively. Importantly, NPS-2143 or RR inhibited both DON-induced food refusal and plasma elevations of the satiety hormones cholecystokinin (CCK) and peptide YY3-36(PYY3-36); cotreatment with both antagonists additively suppressed both anorectic and hormone responses to DON. Taken together, these in vivo data along with prior in vitro findings support the contention that activation of CaSR and TRPA1 contributes to DON-induced food refusal by mediating satiety hormone exocytosis from EEC.
authors.affiliation: College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.|Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: Wenda
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: Hui-Ren
authors.initials: HR
authors.lastname: Zhou
authors.affiliation: Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, 48824, USA. pestka@msu.edu.|Center for Integrative Toxicology, Michigan State University, 234 G.M. Trout Building, East Lansing, MI, 48824-1224, USA. pestka@msu.edu.|Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, 48824, USA. pestka@msu.edu.
authors.forename: James J
authors.initials: JJ
authors.lastname: Pestka
mesh_terms: D000818:Animals; D000855:Anorexia / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D001067:Appetite Depressants / Q000737:chemistry / Q000633:toxicity*; D019167:Appetite Stimulants / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D002766:Cholecystokinin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000097:blood; D004359:Drug Therapy, Combination; D002149:Energy Intake / Q000187:drug effects; D004785:Environmental Pollutants / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005260:Female; D008954:Models, Biological; D010446:Peptide Fragments / Q000819:agonists / Q000037:antagonists & inhibitors / Q000097:blood; D019894:Peptide YY / Q000819:agonists / Q000037:antagonists & inhibitors / Q000097:blood; D011897:Random Allocation; D044169:Receptors, Calcium-Sensing; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D012528:Satiety Response / Q000187:drug effects; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D014255:Trichothecenes / Q000037:antagonists & inhibitors / Q000633:toxicity*
chemical_list: D001067:Appetite Depressants; D019167:Appetite Stimulants; C577923:CASR protein, mouse; D004785:Environmental Pollutants; D010446:Peptide Fragments; D044169:Receptors, Calcium-Sensing; D043562:Receptors, G-Protein-Coupled; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; D014255:Trichothecenes; C475685:Trpa1 protein, mouse; D019894:Peptide YY; C061785:peptide YY (3-36); D002766:Cholecystokinin; C007262:deoxynivalenol
keywords: Anorexia; CCK; Calcium-sensing receptor; Cholecystokinin; Deoxynivalenol; Mycotoxin; PYY3–36; Peptide YY3–36; Transient receptor potential channel