Mediation of altered motility in food protein induced intestinal anaphylaxis in Hooded-Lister rat.

In the Hooded-Lister rat model, food protein induced intestinal anaphylaxis disrupts the migrating motor complex (MMC) and causes an increased frequency of migrating clusters of contractions (MCCs, including giant migrating contractions (GMCs)) and diarrhea. To determine whether mast cell mediators act on enteric neurons to initiate these alterations in motility, rats were sensitized by intraperitoneal injection of 10 micrograms egg albumin (antigen (Ag)). Seven days later two jejunal manometry catheters were implanted 2.5 cm apart. On day 14, motility was recorded in fasted rats before and after intraluminal challenge with 10 mg Ag in 0.5 mL saline, both without and after pretreatment by specific antagonists. Ag challenge of sensitized animals disrupted MMCs and caused an increase in total MCCs (including GMCs) and diarrhea. Atropine or hexamethonium abolished all intestinal motility, including Ag-induced MCCs, GMCs, and diarrhea. At higher doses, agents that inhibit mast cell degranulation, cromoglycate, doxantrazole, and quercetin, did inhibit Ag-induced MCCs, GMCs, and diarrhea, but at the expense of inhibiting normal intestinal motility. Cimetidine and diphenhydramine together inhibited normal cycling of the MMC, but did not abolish Ag-induced MCCs, GMCs, and diarrhea. Methysergide was ineffective, but cinanserin and WAY 100,289 significantly inhibited, and indomethacin most effectively blocked, the Ag-induced disruption of MMCs and the increase in MCCs, GMCs, and diarrhea. Thus, the altered motility and the diarrhea observed after food protein induced luminal challenge of sensitized rats is dependent upon myenteric neuronal circuitry. The mast cell stabilizers doxantrazole and quercetin block the response because of a nonspecific anticholinergic effect. Cinanserin and WAY 100,289 partially inhibit, and indomethacin most effectively blocks, the response, suggesting that activated mast cells release prostaglandins and perhaps 5-hydroxytryptamine, which stimulate the neuronal pathway.