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.
Beubler
E
E
Department of Experimental and Clinical Pharmacology, Karl-Franzens University of Graz, Austria.
Schirgi-Degen
A
A
D000818:Animals; D000880:Anthraquinones / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D003967:Diarrhea / Q000378:metabolism / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007408:Intestinal Absorption; D007419:Intestinal Secretions / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012676:Senna Extract; D000081226:Sennosides; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014867:Water / Q000378:metabolism
D000880:Anthraquinones; D000081226:Sennosides; D012702:Serotonin Antagonists; D014867:Water; D012701:Serotonin; D012676:Senna Extract