Dopamine-induced protection against indomethacin-evoked intestinal lesions in rats--role of anti-intestinal motility mediated by D2 receptors.
Tohru Miyazawa, Masahiro Matsumoto, Shinichi Kato, Koji Takeuchi
Med Sci Monit 2003; 9(2): BR71-77
BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: These results suggest that dopamine protects the small intestine against indomethacin-induced damage, probably by inhibiting the intestinal hypermotility mediated by dopamine D2 receptors.
Keywords: Domperidone - pharmacology, Intestinal Diseases - chemically induced, Intestinal Diseases - physiopathology, Intestinal Diseases - prevention & control, Intestine, Small - pathology