Chronotropic action of 5-hydroxytryptamine (5-HT) on colonic migrating motor complexes (CMMCs) in the isolated mouse colon

The effects of 5-hydroxytryptamine (5-HT) and related drugs on colonic migrating motor complexes (CMMCs) were evaluated in isolated colons from the heterozygotes of pie-bald lethal mice. 5-HT produced a dose-related increase in the frequency of CMMCs without any change in the amplitude or duration of the CMMC contractions themselves. The 5-HT₂ agonist, α-methyl 5-HT, (100 nM–1 μM) increased the frequency of CMMCs whilst the 5-HT₃ agonist, 2-methyl 5-HT, did so at 10 μM. The 5-HT₄ agonist, 5-methoxy dimethyl tryptamine oxalate did not alter the frequency of CMMCs in the concentration range 1 nM–10 μM. The 5-HT₃ receptor antagonist, ondansetron, increased the interval between CMMCs in the concentration range 100 nM–1 μM, whilst the 5-HT₁ receptor antagonist, methiothepin, the 5-HT₂ receptor antagonist, cyproheptadine and the 5-HT₄ receptor antagonist, SDZ 205 557, had no significant effects on the interval between CMMCs in the concentration range 1 nM–10 μM. The effects of 5-HT did not appear to be altered by the presence of ondansetron (1 μM) or cyproheptadine (1 μM). However, in the presence of ondansetron (1 μM), the further addition of cyproheptadine (1 μM) effectively abolished CMMCs. Furthermore, in the combined presence of these antagonists the effects of 5-HT were severely diminished. It is suggested that the frequency of CMMCs may be under the influence of endogenously released 5-HT in this preparation