Enhancement of the cyclic motor activity of the ovine small intestine by lysergic acid derivatives. Mechanism and significance.

The effects of a variety of substances influencing the initiation of cyclic motor events at the gastroduodenal junction were studied in conscious sheep. A significant and long-lasting decrease in the frequency of cyclic events from approximately 100 min to 30-40 min was elicited by the intraduodenal bulb administration of the lysergic acid derivatives methylergonovine and methysergide. This effect was dose-dependent and occurred with smaller dosages than those effective when administered parenterally or more distal in the jejunum. Intraluminal administration of cyproheptadine, fonazine, and metergoline into the duodenal bulb increased the interval between phase III activity. At higher dosages, however, cyproheptadine and metergoline reduced the spiking activity of the antroduodenal junction, without significantly changing the cycle duration of the migrating myoelectric complex on the duodenal bulb or jejunum. After administration of cyproheptadine, fonazine, and metergoline, the cycling activity of the duodenojejunum was irregular for 1-2 days. These findings are compatible with a resetting of the enteric biological clock at a faster rhythm and suggest a selective action via an enteric serotoninergic mechanism involved in the normal pacing of the cyclic motor events of the gut.