Changes in colonic motility induced by sennosides in dogs: evidence of a prostaglandin mediation.

Abstract

SUMMARY The effects of sennosides on colonic motility were investigated in eight conscious dogs chronically fitted with two strain gauge transducers in the proximal colon, an intracolonic silicone catheter and a polyethylene catheter implanted in a branch of the right colonic artery. Oral sennosides (30 mg/kg) inhibited colonic motility for 12 to 18 h after a three to six hours delay, and associated with giant contractions and diarrhoea. The minimal oral dose of sennosides to produce such changes varied from 5 to 15 mg/kg. Intracolonic sennosides at the minimal effective dose and at 30 mg/kg reproduced the effects of oral sennosides, but with a shorter latency (0.5-45 h).Intracolonic PGE2 (100 tg/kg) in viscous gel medium or intra-arterial PGE2 (10 /tgfh) inhibited colonic motility and induced giant contractions often associated with defecation. The colonic motor changes induced by intracolonic sennosides at the minimal effective dose, but not those induced by intracolonic PGE2, were blocked by intra-arterial indomethacin (10 [&g/h) or piroxicam (5 [tgfh). These results suggest that colonic motor actions of sennosides are mediated through a local prostaglandins synthesis, as they were blocked by cyclooxygenase inhibitor and reproduced by PGE2.Sennosides, the main laxative components of senna extracts, which chemically belong to the anthraquinones, are known to induce fluid secretion in the colon'2 and to modify colonic motility.-5 Because of their dianthrone-13-glycoside structure a bacterial degradation of sennosides is necessary to obtain active laxative metabolites.6 For this reason sennosides are pharmacologically inert in the upper gastrointestinal tract and have an action localised at the colonic level.The effects of sennosides on colonic motility remain controversial: a stimulation of peristaltic pressure waves has been reported in human after intraluminal administration through a colostomy3 whereas a reduction of the intracolonic pressure' and a long lasting inhibition of the colonic myoelectrical activity4 have been described after oral administration in man and dogs respectively. These discrepanAddress for correspondence: Dr J Fioramonti, Station de Pharmacologie, INRA, 180 chemin de Tournefeuille, 31300 Toulouse, France. Received for publication 11 March 1988. cies may be attributed to differences in methodology, the intraluminal application not being a classical route and the electromyography technique not taking into account the amplitude of contractions. The first aim of this study was, to describe the changes in colonic motility induced by oral administration of pure sennosides in the dog, a species characterised by a well defined colonic motor profile.7The secretory effects of sennosides have been shown to be mediated through a prostaglandin synthesis as they are blocked by indomethacin.28 Prostaglandins are also known to modify colonic motility. Prostaglandin E has been found to induce a persistaltic activity in isolated longitudinal strips of colon associated with a relaxation of circular mu...

Endoluminal Instillation of Bisacodyl inPatients with Severe (Slow Transit Type)Constipation Is Useful to Test Residual ColonicPropulsive Activity

“…As a pharmacological test, bisacodyl was chosen in preference to other stimulant laxatives because some, such as sennosides, require preliminary bacterial hydrolysis to act [29, 30]. However, bisacodyl and sennosides probably display similar mechanisms of action (prostaglandin-mediated) since, at least in experimental animal studies, such mechanisms have been demonstrated [31, 32]. More recent studies also suggest that the effect of bisacodyl on intestinal transport may be, at least in part, mediated through nitric oxide inhibition [33].…”

Effects of Long-Term Sennoside Treatment on in vitro Motility of Rat Colon

“…As acute experiments in rat ascending colon treated locally with rhein Na or orally with sennosides (50 or 100 mg/kg) 5 h before also showed a reduction in maximal contractile force and fre quency of contractions [13], these effects are interpreted as a residual pharmacological ac tivity due to high-dose treatment. Electromyo graphic measurements in rat colon in vivo revealed a decreased motility index after a high dose senna preparation within 2-4 h and total recovery was not observed within 20 h [4], In dogs fitted with strain gauge transduc ers, sennosides inhibited colonic motility in general, but sometimes giant contractions ap peared and were often associated with defaeca- tion [14]. In man, propulsive activity was the main feature observed after sennosides [6], Other experiments in the isolated, vascularly perfused complete large intestine of the rat showed a transient increase in colonic excitability and propulsive activity only after a very high concentration of rhein adminis tered luminally [15].…”

In vitro Effects of Sennoside on Contractile Activity and Fluid Flow in the Perfused Large Intestine of the Rat

“…The nature of the underlying mechanism by which senna alters motility is largely un known [ 1 ], but the effects are simulated by the administration of PGE2 [17], The response is sensitive to the cyclooxygenase inhibitor indometacin. However, indometacin only par tially blocks senna-induced diarrhoea, so oth er mechanisms are also likely to be involved [18].…”