Chronic low-level administration of diquat increases the nociceptive response to gastric distension in rats: role of mast cells and tachykinin receptor activation.
Dietary factors can modulate visceral sensitivity and are suggested to interact with neuroimmune pathways. To determine whether daily low-level exposure to a food contaminant (diquat) alters sensitivity to gastric distension (GD) and the role of mast cells and tachykinin receptors activation, two series of experiments were conducted in eight groups of eight male Wistar rats (200-250 g) receiving daily doses of either diquat (0.1 mg/kg per day orally) or water for 21 days. In the first series, rats were sacrificed at the end of treatments and the gastric mucosal mast cell (MMC) number was histologically quantified. In the second series, after 21 days of treatment the cardiovascular depressor (CVD) response and corresponding gastric volumes were recorded under GD (from 10 to 40 mmHg). Doxantrazole (5 mg/kg intraperitoneally (i.p.)), a mast cell stabilizer, and SR 140333 (1 mg/kg i.p.) and MEN 11420 (0.1 mg/kg intravenously), respectively NK1 and NK2 receptor antagonists, were administered before GD. Before and after GD, blood samples were taken to measure blood histamine and the gastric MMC number was determined after sacrifice. Diquat treatment increased the MMC number. In diquat-treated rats, GD increased the CVD response and blood histamine level and induced MMC degranulation. Doxantrazole did not modify the hypersensitivity to GD but prevented mast cell degranulation. Both NK1 and NK2 receptor antagonists blocked the enhanced CVD response induced by diquat and prevented mast cell degranulation. None of the drugs had any effect in control animals. Prolonged exposure to a food contaminant at doses possibly found in food increases gastric sensitivity to distension, activates tachykinin receptors and results in MMC degranulation after GD.
Anton
P M
PM
Neuro-Gastroenterology and Nutrition Unit, INRA, 180 chemin de Tournefeuille, BP3, 31931 Cedex 09, Toulouse, France.
Theodorou
V
V
Fioramonti
J
J
Bueno
L
L
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001993:Bronchodilator Agents / Q000494:pharmacology; D004178:Diquat / Q000494:pharmacology*; D005506:Food Contamination; D013271:Gastric Dilatation / Q000503:physiopathology*; D006540:Herbicides / Q000494:pharmacology*; D006632:Histamine / Q000097:blood; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D018041:Receptors, Neurokinin-2 / Q000378:metabolism; D013270:Stomach / Q000294:innervation / Q000502:physiology; D013892:Thioxanthenes / Q000494:pharmacology; D044004:Xanthones
D001993:Bronchodilator Agents; D006540:Herbicides; C107754:MEN 11420; D010456:Peptides, Cyclic; D010726:Phosphodiesterase Inhibitors; D010880:Piperidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D013892:Thioxanthenes; D044004:Xanthones; C085215:SR 140333; D006632:Histamine; D004178:Diquat; C010134:doxantrazole