Alteration of cholinergic, purinergic and sensory neurotransmission in the mouse colon of food allergy model.
It is well known that intestinal anaphylaxis results in a disturbed intestinal motility. It is hypothesized that the chronic intestinal anaphylaxis-induced changes in the enteric neuronal circuitry cause intestinal motor malfunctions. However, detailed mechanisms largely remain unclear. The aim of this study was to investigate the pathophysiological role of ATP, which acts as a non-cholinergic neurotransmitter and a neuroimmune modulator, in a disturbed intestinal motility of food allergy (FA). The FA mice developed allergic diarrhea accompanied with chronic inflammation and mast cell hyperplasia in the colon. The excised proximal colons (PCs) were suspended in the longitudinal direction in organ baths. In the PCs precontracted by KCl (50 mM), contractile responses to exogenous ATP (1 mM) were significantly (P < 0.01) higher in FA mice (34.2% of KCl-induced precontractions) as compared to control mice (17.2%). Pretreatment with P2 purinoceptor antagonists [suramin and PPADs] significantly (P < 0.01) reduced the ATP-evoked contractions to 7.7% and 1.5% in FA and control PCs, respectively. Furthermore, in the presence of inhibitors of cholinergic nerves and capsaicin-sensitive sensory nerves the electrical field stimulation (EFS; 10Hz)-evoked contractions were significantly (P < 0.05) higher in FA mice (65.8% of EFS-evoked maximum contractions, n = 6) than those in control mice (47.9%, n = 6). In addition, cumulative application of suramin and PPADs further inhibited EFS-induced contractions by 21.7% in FA mice (n = 6, P < 0.01) and 8.7% in control mice (n = 6, P < 0.05). Thus, the present study suggests that the sustained alteration in cholinergic, purinergic and sensory neurotransmission contribute to the disturbed motility during the chronic intestinal anaphylaxis.
Leng
Yuxin
Y
Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
Yamamoto
Takeshi
T
Kadowaki
Makoto
M
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000378:metabolism; D003106:Colon / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005512:Food Hypersensitivity / Q000150:complications / Q000473:pathology*; D005769:Gastrointestinal Motility / Q000187:drug effects; D018738:Hexamethonium / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018733:Nicotinic Antagonists / Q000494:pharmacology; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018733:Nicotinic Antagonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D018738:Hexamethonium; D011732:Pyridoxal Phosphate; D013498:Suramin; D001285:Atropine; D000109:Acetylcholine; D002211:Capsaicin