Serotonin Antagonists Inhibit Sennoside-lnduced Fluid Secretion and Diarrhea

Abstract

The aim of this study was to investigate whether 5-hydroxy-tryptamine (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 μg/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.

Experimental study of antidiarrheal activity of Salicairine®

“…Salicairinew antidiarrheal activity could also be due to inhibition of PGE, effect. It could be linked to serotoninergic system because serotonin has been demonstrated as involved in the secretory response to laxatives [4], but likely not to adrenergic system because if catecholamines stimulate sodium and chloride absorption from the intestine by interacting with a(2)-adrenergic receptors on enterocytes [ 171, clonidine delays normal small intestinal transit in the rat [ 161 and inhibits defecation in basal conditions [ 6 ] , which it is not the case for Salicairine@. Finally, since Salicairine@ did not show antipropulsive effects on normal intestine, it seems unlikely that its antidiarrheal effect could be due to an opioid activity, and no such effect has yet been reported.…”

Mast cell expression of the serotonin1Areceptor in guinea pig and human intestine

“…Aside from a role as an ENS neurotransmitter, 5-HT is a recognized paracrine signal released in large amounts from enterochromaffin cells that reside in the intestinal mucosa (4,12,17,46,55). As a paracrine signal, it spreads in diffuse fashion to bind with its receptors on enteric neurons and intramural sensory afferents.…”

“…Brushing of luminal contents past the mucosa is a mechanical stimulus for release from enterochromaffin cells, as implied by results from studies on human enterochromaffin cell-derived BON cells (29). Noxious stimulation by laxatives (e.g., senna), chemotherapeutic agents, or injurious ionizing radiation can evoke release (4,12,17). In view of the probability that enteric mast cells are exposed to 5-HT arriving from multiple sources, we aimed to investigate its actions on release of mast cell mediators and identify the receptors that might be involved.…”

Berberine increases the expression of NHE3 and AQP4 in sennosideA-induced diarrhoea model

“…BALB/c mice (male or female, 20-22 g) were used in this study. Sennoside, a well-known laxative, has been widely used to induce diarrhoea in mice, rats and dogs [23][24][25][26]. Mice were repeatedly given 20 mg/kg sennosideA (diluted in ddH 2 O, ChenDu mansite pharmaceutical co) with intragastric feeding needles twice a day in the diarrhoea group, and those with profuse liquid stools were recorded as diarrhoea-positive animals.…”