Oosterbosch L, von der Ohe M, Valdovinos M A, Kost L J, Phillips S F, Camilleri M
Gastroenterology Research Unit, Mayo Clinic, Rochester, MN 55905.
Gut. 1993 Jun;34(6):794-8. doi: 10.1136/gut.34.6.794.
The aim was to investigate the action of serotonin (5HT) on function of the ileocolonic junction (ICJ) in vivo. In anaesthetised rats, models were developed to study the effects of intra-aortic (ia) serotonin on ileocolonic and colonic transit, and the effects on transit of a number of 5HT receptor antagonists. In the first series of experiments, a bolus of saline labelled with 99mTc DTPA was instilled 20 cm proximal to the ICJ and transit was assessed three hours later by the geometric centre of the spread of isotope. In the second series, similar techniques were used on the postcaecal colon and transit assessed two hours later. In the third series of experiments, the effects of ia 5HT on ileal net fluid flux was evaluated by standard perfusion experiments with 14C polyethylene glycol (PEG) 4000 as a non-absorbable marker in rat plasma-like electrolyte solution. Compared with ia saline, 5HT accelerated ICJ transit significantly (p < 0.05). This acceleration was comparable with the effect of ia bethanechol. The effects of 5HT on ICJ transit were inhibited by the intraperitoneal (ip) infusion of atropine, the 5HT receptor antagonists, methysergide, ketanserin, zacopride, and the 5HT4 agonist, SC53116. Methysergide, zacopride, and SC53116 given with ia 5HT slowed ICJ transit to rates below those of ia saline alone. When these same agents were given together with ia saline, the ICJ transit was not significantly altered. Serotonin, at the dose that accelerated ICJ transit, did not significantly alter colonic transit or ileal fluid transport. In conclusion, 5HT is a potent pharmacological stimulant of transit across the rat ICJ in vivo; the action of 5HT is mediated partly through muscarinic neurones and several 5HT receptor subtypes.
目的是研究5-羟色胺（5HT）对体内回结肠连接部（ICJ）功能的作用。在麻醉大鼠中，建立模型以研究主动脉内（ia）注射5HT对回结肠和结肠转运的影响，以及多种5HT受体拮抗剂对转运的影响。在第一系列实验中，将一剂用99mTc DTPA标记的生理盐水注入ICJ近端20厘米处，并在三小时后通过同位素扩散的几何中心评估转运情况。在第二系列实验中，在后盲肠结肠采用类似技术，并在两小时后评估转运情况。在第三系列实验中，通过在大鼠血浆样电解质溶液中使用14C聚乙二醇（PEG）4000作为不可吸收标记物的标准灌注实验，评估ia 5HT对回肠净液体通量的影响。与ia注射生理盐水相比，5HT显著加速了ICJ转运（p < 0.05）。这种加速与ia注射氨甲酰甲胆碱的效果相当。腹腔内（ip）注射阿托品、5HT受体拮抗剂美西麦角、酮色林、扎考必利以及5HT4激动剂SC53116可抑制5HT对ICJ转运的影响。与ia注射5HT同时给予美西麦角、扎考必利和SC53116可使ICJ转运减慢至低于单独ia注射生理盐水的速率。当这些相同药物与ia注射生理盐水同时给予时，ICJ转运没有显著改变。在加速ICJ转运的剂量下，5HT没有显著改变结肠转运或回肠液体运输。总之，5HT是体内大鼠ICJ转运的一种强效药理学刺激物；5HT的作用部分通过毒蕈碱神经元和几种5HT受体亚型介导。
