A direct and an indirect action of 5-hydroxytryptamine on the distal part of the isolated colon of the rat.

Abstract

Abstract The motor response of 5-hydroxytryptamine (5-ht) on the distal part of the isolated rat colon was investigated by constructing dose: response curves to 5-ht, acetylcholine and nicotine; these were repeated in the presence of different antagonists and an anticholinesterase. Hyoscine abolished the responses to acetylcholine, almost completely blocked the effect of nicotine, but reduced the contractions to 5-ht only to about half of the original level. The anticholinesterase NN’-diisopropylphosphorodiamidic fluoride (mipafox) potentiated the responses to acetylcholine, 5-ht or nicotine. Procaine and cocaine inhibited to the same extent the large doses of 5-ht, but had no effect on the small doses. Both drugs reduced the contractions with nicotine. Three ganglion-blocking agents were used. Hexamethonium had no effect on acetylcholine or 5-ht, but antagonised nicotine. Mecamylamine had no effect on acetylcholine; it blocked the responses to nicotine and reduced the large doses of 5-ht. The action of dimethylphenylpiperazinium on the three agonists was similar to that of mecamylamine. 2-Bromolysergic acid diethylamide had no effect on the responses to acetylcholine, but reduced equally the contractions due to 5-ht and nicotine. It was concluded that 5-ht acted indirectly by stimulating the intramural parasympathetic ganglia and directly by an action on the muscle fibres. The direct action was pronounced with small doses, the indirect action with higher doses of 5-ht.