Scott R B, Tan D T
Intestinal Disease Research Unit, University of Calgary, AB, Canada.
Can J Physiol Pharmacol. 1996 Mar;74(3):320-30.
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.
在长爪沙鼠模型中，食物蛋白诱导的肠道过敏反应会破坏移行性运动复合波（MMC），并导致移行性收缩簇（MCC，包括巨大移行性收缩（GMC））的频率增加以及腹泻。为了确定肥大细胞介质是否作用于肠神经元以引发这些运动改变，通过腹腔注射10微克卵清蛋白（抗原（Ag））使大鼠致敏。7天后，在相距2.5厘米处植入两根空肠测压导管。在第14天，在禁食大鼠中，分别在腔内注射含10毫克Ag的0.5毫升生理盐水前后记录运动情况，且均在使用特异性拮抗剂预处理前后进行记录。对致敏动物进行Ag激发会破坏MMC，并导致总MCC（包括GMC）增加以及腹泻。阿托品或六甲铵可消除所有肠道运动，包括Ag诱导的MCC、GMC和腹泻。在较高剂量下，抑制肥大细胞脱颗粒的药物色甘酸、多克沙唑和槲皮素确实能抑制Ag诱导的MCC、GMC和腹泻，但代价是抑制正常肠道运动。西咪替丁和苯海拉明共同抑制MMC的正常循环，但不能消除Ag诱导的MCC、GMC和腹泻。麦角新碱无效，但辛那色林和WAY 100,289能显著抑制，吲哚美辛最有效地阻断了Ag诱导的MMC破坏以及MCC、GMC和腹泻的增加。因此，食物蛋白诱导致敏大鼠腔内激发后观察到的运动改变和腹泻依赖于肌间神经回路。肥大细胞稳定剂多克沙唑和槲皮素由于非特异性抗胆碱能作用而阻断反应。辛那色林和WAY 100,289部分抑制，吲哚美辛最有效地阻断反应，这表明活化的肥大细胞释放前列腺素，可能还有5-羟色胺，从而刺激神经通路。
