Serotonin antagonists inhibit sennoside-induced fluid secretion and diarrhea

The aim of this study was to investigate whether 5-hydroxytryptamine (serotonin, 5-HT) is involved in the mediation of sennoside-induced colonic fluid secretion and diarrhea. Oral administration of purified sennosides (25, 40 and 64 mg/kg) dose-dependently reversed net fluid absorption to net fluid secretion, enhanced the incidence of diarrhea and stimulated the release of 5-HT into the colonic lumen from 7.1 to 17.3 ng/g wet weight. The 5-HT2 antagonist ketanserin and the 5-HT3 antagonist tropisetron dose-dependently but only partially reduced sennoside (40 mg/kg)-induced fluid secretion whereas the 5-HT3 antagonist granisetron dose-dependently reduced and at 300 micrograms/kg totally abolished sennoside-induced secretion. Granisetron, but not ketanserin and tropisetron, reduced the incidence of diarrhea in sennoside-treated rats, indicating the involvement of 5-HT also in acceleration of large intestinal transit. It is concluded that 5-HT is an important mediator both of sennoside-induced fluid secretion in the rat colon and of diarrhea.