Miyazawa Tohru, Matsumoto Masao, Kato Shinichi, Takeuchi Koji
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, Japan.
Med Sci Monit. 2003 Feb;9(2):BR71-7.
Although it is known that dopamine prevents various gastrointestinal lesions, the underlying mechanism remains unclear. In the present study, we examined the protective effect of dopamine on indomethacin-induced small intestinal lesions, in relation to intestinal hypermotility.
MATERIAL/METHODS: Male SD rats received indomethacin (10 mg/kg) subcutaneously (s.c.), and the small intestine was examined for lesions 24 hr later. Dopamine (1-10 mg/kg) or atropine (3 mg/kg) was administered s.c. twice, 30 min before and 8 hr after indomethacin, while sulpiride (3 mg/kg) and domperidone (3 mg/kg), the dopamine D2 receptor antagonists, or yohimbine (10 mg/kg), the alpha2-adrenoceptor antagonist, were administered s.c. twice, 30 min before each dosing of dopamine. Intestinal motility was measured using a balloon under urethane anesthesia.
Indomethacin caused severe lesions in the small intestine, mainly both the jejunum and ileum. The intestinal ulcerogenic response to indomethacin was dose-dependently prevented by dopamine as well as atropine. The protective effect of dopamine was almost totally antagonized by domperidone and sulpiride but not by yohimbine. On the other hand, indomethacin markedly enhanced intestinal motility, and the hypermotility response was also prevented by dopamine as well as atropine. Both sulpiride and domperidone, but not yohimbine, also antagonized the inhibitory effect of dopamine on the indomethacin-induced intestinal hypermotility.
These results suggest that dopamine protects the small intestine against indomethacin-induced damage, probably by inhibiting the intestinal hypermotility mediated by dopamine D2 receptors.
尽管已知多巴胺可预防多种胃肠道损伤，但其潜在机制仍不清楚。在本研究中，我们研究了多巴胺对吲哚美辛诱导的小肠损伤的保护作用，并探讨其与肠道运动亢进的关系。
材料/方法：雄性SD大鼠皮下注射吲哚美辛（10mg/kg），24小时后检查小肠损伤情况。多巴胺（1-10mg/kg）或阿托品（3mg/kg）在吲哚美辛注射前30分钟和注射后8小时各皮下注射一次，而多巴胺D2受体拮抗剂舒必利（3mg/kg）和多潘立酮（3mg/kg），或α2-肾上腺素能受体拮抗剂育亨宾（10mg/kg），在每次注射多巴胺前30分钟各皮下注射一次。在乌拉坦麻醉下使用气囊测量肠道运动。
吲哚美辛导致小肠严重损伤，主要发生在空肠和回肠。多巴胺和阿托品均可剂量依赖性地预防吲哚美辛引起的肠道溃疡形成反应。多潘立酮和舒必利几乎完全拮抗了多巴胺的保护作用，而育亨宾则无此作用。另一方面，吲哚美辛显著增强了肠道运动，多巴胺和阿托品也可预防这种运动亢进反应。舒必利和多潘立酮均拮抗了多巴胺对吲哚美辛诱导的肠道运动亢进的抑制作用，而育亨宾则无此作用。
这些结果表明，多巴胺可能通过抑制多巴胺D2受体介导的肠道运动亢进，保护小肠免受吲哚美辛诱导的损伤。
