L-dopa is protective against indomethacin-induced small intestinal ulceration in the rat: Possible role of an α-2-adrenergic mechanism

Dopaminergic agents ameliorate experimentally induced gastroduodenal mucosal injury, but there is no information about their effect on small intestinal mucosa. We studied the effect of L-dopa and related substances on indomethacin-induced intestinal ulceration in the rat. Ulceration was produced by s.c. injection of 30 mg/kg indomethacin, 30 min after refeeding fasted rats. Total ulcer area was measured 24 hrs after indomethacin administration. L-dopa, 5 mg/kg given in two divided doses 5 h apart, starting 30 minutes before administration of indomethacin, was found to protect the small bowel mucosa against indomethacin- induced damage (ulcer area 122±5.5vs 224.2±5.4 mm², mean±SEM, p<0.006). Administration of 5mg/kg haloperidol, a dopa antagonist, did not abolish the protective effect of L-dopa. On the other hand, yohimbine, and α-2-adrenoreceptor antagonist, almost completely abolished the protective effect (180.4±5.3 vs 122±5.5, p<0.004). Clonidine 20μg/kg, an α-2-adrenoreceptor agonist, closely mimicked the protective effect of L-dopa (141.5±10.9 vs 224.2±5.4, p<0.006). All drugs were give i.p. in two divided doses, at the same schedule as described for L-dopa. The results demonstrate that L-dopa has a protective effect on indomethacin-induced small bowel injury in the rat. The protective effect is probably mediated through stimulation of α-2-adrenoreceptors.