The mycotoxin, deoxynivalenol, delays gastric emptying through serotonin-3 receptors in rodents.
The effects of the trichotecene mycotoxin, deoxynivalenol, on gastric emptying and intestinal propulsion in mice and rats and gastrointestinal myoelectrical activity in rats were investigated. Gastric emptying and intestinal transit were evaluated after gavage with a milk meal containing a marker (51CrO4Na2) and radio-activity was counted in the stomach and 10 segments of the small intestine. The myoelectrical activity of the antrum, duodenum and jejunum was assessed by implanting electrodes for long-term electromyographic recordings. Deoxynivalenol given orally (50-1000 micrograms/kg) but not i.c.v. (5 micrograms/kg) 10 min before the test meal inhibited gastric emptying in a dose-related manner. Intestinal propulsion was reduced for the highest dose (1000 micrograms/kg) only. The inhibition of gastric emptying induced by deoxynivalenol was antagonized by ondansetron and granisetron given s.c. (50 micrograms/kg) but not by ondansetron i.c.v. (10 micrograms/kg). Metoclopramide, domperidone (1 mg/kg s.c.), methysergide, ritanserin and cisapride (2 mg/kg s.c.) did not modify the deoxynivalenol-induced inhibition of gastric emptying. In rats, gavage with a 2.5-ml milk meal increased the frequency of antral spike bursts from 1.9 +/- 0.9/min in the fasted state to 4.7 +/- 0.4/min and disrupted intestinal migrating motor complexes for 84.9 +/- 10.8 min. Oral administration of deoxynivalenol (50-100 micrograms/kg) 10 min before the meal did not modify the frequency of antral spike bursts but induced migrating motor complexes on the small intestine after the meal. This effect was reversed by ondansetron (10 micrograms/kg s.c.). It was concluded that, in rodents, deoxynivalenol inhibits gastric emptying by inducing intestinal migrating motor complexes through a peripheral action at the serotonin-3 receptors.
Department of Pharmacology, Institut National de la Recherche Agronomique, Toulouse, France.
J
J
Fioramonti
C
C
Dupuy
J
J
Dupuy
L
L
Bueno
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005746:Gastric Emptying / Q000187:drug effects*; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009183:Mycotoxins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists; D014255:Trichothecenes / Q000037:antagonists & inhibitors / Q000633:toxicity*
D009183:Mycotoxins; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014255:Trichothecenes; C007262:deoxynivalenol