Inhibitory action of 5-hydroxytryptamine on propulsive activity of the guinea-pig isolated colon

The effects of 5-hydroxytryptamine (5-HT) and its receptor subtype agonists on spontaneous propulsive activities of the segment, and on changes in tension of the muscle strips were examined in the guineapig isolated distal colon. 5-HT, 5-carboxamidotryptamine (5-CT), alpha-methyl-5-HT and t-methoxytryptamine (5-MeOH), applied to the serosal side of the segment, inhibited spontaneous propulsive activities, but 2-methyl-5-HT did not. On the indomethacin-treated segment, 5-HT and its receptor subtype agonists all stimulated propulsive activity. 5-HT, 5-CT, alpha-methyl-5-HT and 5-MeOH relaxed circular muscle strips, which were inhibited in the presence of tetrodotoxin. However, these agonists showed contractile effects on the indomethacin-treated circular muscle strips. These results suggest that 5-HT may inhibit spontaneous propulsive activities of the colonic segment via release of endogenous PGs (e.g., E and I types) in the circular muscle cells mediated by an inhibitory neurotransmitter, which release was stimulated by 5-HT1-like 5-HT2 and 5-HT4 receptors on the myenteric neurones in the circular muscle layer.