Model of rapid gastrointestinal transit in dogs: effects of muscarinic antagonists and a nitric oxide synthase inhibitor
Model of rapid gastrointestinal transit in dogs: effects of muscarinic antagonists and a nitric oxide synthase inhibitor
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DOI：
10.1046/j.1365-2982.2002.00357.x
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发表时间：
2002-10-01
影响因子：
3.5
通讯作者：
Phillips, SF
中科院分区：
文献类型：
--
作者：
Chiba, T;Bharucha, AE;Phillips, SF
我们的目的是建立快速胃肠道运输的犬模型，并测试毒蕈碱受体拮抗剂（阿托品、哌仑西平、AF-DX116 和达非那新）和 NOS 抑制剂 l-硝基-N-精氨酸 (l-NNA) 在此模型中的作用。对于胃排空和小肠转运，将 (99m) Tc 标记的 DTPA 添加到含有 2.4 g 氢氧化镁的脱脂牛奶 (236 mL) 中。通过放置在胶囊中的 (111) In 标记珠子来测量区域结肠转运，该胶囊在近端结肠中释放同位素。定期进行闪烁扫描并计算传输指数。药物通过静脉注射给药。胃排空、小肠和结肠运输很快。阿托品和达非那新（选择性 M (3) 拮抗剂）可延迟胃排空和结肠转运，而选择性 M (1) 和 M (2) 毒蕈碱拮抗剂则不会。毒蕈碱阻滞剂不会减慢小肠运输。 l-NNA 延迟小肠和结肠运输，但不会减慢胃排空。建立了适合止泻药临床前研究的模型。 M (3) 受体在胃排空和结肠转运的控制中很重要，NOS 抑制会减慢小肠和结肠转运。
Our aims were to establish a canine model of rapid gastrointestinal transit, and to test the effects of muscarinic receptor antagonists (atropine, pirenzepine, AF-DX116, and darifenacin), and an NOS inhibitor, l-nitro-N-arginine (l-NNA) in this model. For gastric emptying and small bowel transit, (99m) Tc-labelled DTPA were added to a meal of skimmed milk (236 mL) that contained 2.4 g of magnesium hydroxide. Regional colonic transit was measured by (111) In-labelled beads placed in a capsule that released isotope in the proximal colon. Scintiscans were taken at regular intervals and indices of transit were calculated. Drugs were administrated intravenously. Gastric emptying, small bowel and colonic transit were rapid. Atropine and darifenacin (a selective M (3) antagonist) delayed gastric emptying and colonic transit, the selective M (1) and M (2) muscarinic antagonists did not. The muscarinic blockers did not slow small bowel transit. l-NNA delayed small bowel and colonic transit but did not slow gastric emptying. A model suitable for the preclinical study of antidiarrhoeals was established. M (3) receptors are important in the control of gastric emptying and colonic transit, and NOS inhibition slowed small bowel and colonic transit.