Chiba T, Bharucha A E, Thomforde G M, Kost L J, Phillips S F
Division of Gastroenterology, Mayo Clinic and Mayo Foundation, Rochester, MA 55905, USA.
Neurogastroenterol Motil. 2002 Oct;14(5):535-41. doi: 10.1046/j.1365-2982.2002.00357.x.
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, 99mTc-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 by111In-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 M3 antagonist) delayed gastric emptying and colonic transit, the selective M1 and M2 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. M3 receptors are important in the control of gastric emptying and colonic transit, and NOS inhibition slowed small bowel and colonic transit.
我们的目的是建立一种快速胃肠转运的犬模型，并在该模型中测试毒蕈碱受体拮抗剂（阿托品、哌仑西平、AF-DX116和达非那新）以及一种一氧化氮合酶（NOS）抑制剂L-硝基-N-精氨酸（L-NNA）的作用。对于胃排空和小肠转运，将99mTc标记的二乙三胺五乙酸加入到含有2.4 g氢氧化镁的脱脂奶（236 mL）餐中。通过置于胶囊中的111In标记微珠来测量结肠局部转运，该微珠在结肠近端释放同位素。定期进行闪烁扫描并计算转运指标。药物通过静脉给药。胃排空、小肠和结肠转运均很快。阿托品和达非那新（一种选择性M3拮抗剂）延迟了胃排空和结肠转运，而选择性M1和M2毒蕈碱拮抗剂则没有。毒蕈碱阻滞剂并未减慢小肠转运。L-NNA延迟了小肠和结肠转运，但未减慢胃排空。建立了一种适用于止泻药临床前研究的模型。M3受体在胃排空和结肠转运的控制中起重要作用，抑制NOS可减慢小肠和结肠转运。
