Effects of 5-HT2B, 5-HT3 and 5-HT4 receptor antagonists on gastrointestinal motor activity in dogs

Abstract

To study the effects of 5-hydroxytryptamine (5-HT) receptor antagonists on normal colonic motor activity in conscious dogs. Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs before and after 5-HT2B, 5-HT3 and 5-HT4 receptor antagonist administration. The force transducers were implanted on the serosal surfaces of the gastric antrum, terminal ileum, ileocecal sphincter and colon. Test materials or vehicle alone was administered as an intravenous bolus injection during a quiescent period of the whole colon in the interdigestive state. The effects of these receptor antagonists on normal gastrointestinal motor activity were analyzed. 5-HT2B, 5-HT3 and 5-HT4 receptor antagonists had no contractile effect on the fasting canine terminal ileum. The 5-HT3 and 5-HT4 receptor antagonists inhibited phase III of the interdigestive motor complex of the antrum and significantly inhibited colonic motor activity. In the proximal colon, the inhibitory effect was dose dependent. Dose dependency, however, was not observed in the distal colon. The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity. The 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor activity. The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.