Mechanisms of Action of Laxative Drugs

Gullikson, Gary W.; Bass, Paul

doi:10.1007/978-3-642-69508-7_11

Cited by 10 publications

(6 citation statements)

References 215 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Assay of NO synthase confirmed that magnesium sulphate stimulated NO synthase activity in the intestine and that L-NAME can block this effect. The NO synthesis precursor, L-arginine, and the NO donating compound, IMN, both D-NAME -1.10±0.07 0.14 ± 0.07 0.14 ±0.09 The laxative response to magnesium sulphate results from effects on gut smooth muscle (enhancement of transit) and mucosal electrolyte transport (Gullikson & Bass, 1984;Stewart et al, 1975). The inhibition of electrolyte absorption or stimulation of secretion causes the accumulation of fluid in the gut lumen, which is what we observed in the present experiments.…”

Section: Discussionmentioning

confidence: 99%

“…and D-NAME (25mg kg-', i.p.) on magnesium The laxative response to magnesium sulphate results from effects on gut smooth muscle (enhancement of transit) and mucosal electrolyte transport (Gullikson & Bass, 1984;Stewart et al, 1975). The inhibition of electrolyte absorption or stimulation of secretion causes the accumulation of fluid in the gut lumen, which is what we observed in the present experiments.…”

Section: Discussionmentioning

confidence: 99%

“…NO is an intestinal secretagogue (Tamai & Gaginella, 1994) and it relaxes intestinal smooth muscle (Boeckxstaens et al, 1993;Grider, 1993;Stark et al, 1993). This muscle relaxant effect is likely to enhance intestinal transit and contribute to a laxative/diarrhoeal effect (Gullikson & Bass, 1984).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nitric oxide as a mediator of the laxative action of magnesium sulphate

Izzo

Gaginella

Mascolo

et al. 1994

British J Pharmacology

View full text Add to dashboard Cite

1Magnesium sulphate was studied for its effects on diarrhoea, fluid secretion, gastrointestinal transit and nitric oxide (NO) synthase activity in rats. 2 At a dose of 2 g kg-orally magnesium sulphate produced diarrhoea that was delayed in onset and intensity in a dose-related manner by the NO synthase inhibitor N0-nitro-L-arginine methyl ester (L-NAME). This was prevented by the NO precursor, L-arginine and the NO donating compound, isosorbide-5-mononitrate (IMN). 3 Nitric oxide synthase activity was stimulated in gut tissue from rats given magnesium sulphate and this was inhibited by L-NAME. Dexamethasone (1 mg kg-', i.p.), an inhibitor of inducible NO synthase, had no effect on magnesium sulphate-induced diarrhoea. 4 Magnesium sulphate stimulated fluid and electrolyte accumulation in the intestinal lumen; these effects were prevented by L-NAME but not D-NAME. 5 Gastrointestinal transit of a non-absorbable marker (charcoal suspension) was increased by oral magnesium sulphate from a mean value of 54.1% to 72.9% (P<0.01), and this was prevented by pretreatment with L-NAME. 6 The results demonstrate that oral magnesium sulphate produces diarrhoea in rats by increasing the accumulation of fluid in the intestinal lumen and enhancing flow from the proximal to distal intestine. The mechanism involves release of NO, probably through stimulation of the constitutive form of NO synthase. Whether or not the effects of magnesium sulphate are due to an osmotic action or an intrinsic effect of the magnesium or sulphate ions cannot be determined from these experiments.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Nitric oxide as a mediator of the laxative action of magnesium sulphate

Izzo

Gaginella

Mascolo

et al. 1994

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Castor oil (ricinoleic acid) affects electrolyte transport and smooth muscle contractility in the intestine (Gullikson & Bass, 1984;Nell & Rummel, 1984;Binder, 1977;Izzo et al, 1993b;Gaginella, 1994). The precise mechanism of action of this common laxative remains elusive, partly because of its multiple effects on the gut.…”

Section: Introduction Methodsmentioning

confidence: 99%

Dissociation of castor oil‐induced diarrhoea and intestinal mucosal injury in rat: effect of N^G‐nitro‐L‐arginine methyl ester

Capasso

Mascolo

Izzo

et al. 1994

British J Pharmacology

108

View full text Add to dashboard Cite

1 Castor oil (2 ml orally) produced diarrhoea in rats 1-7 h after challenge, which was associated with gross damage to the duodenal and jejunal mucosa. 2 The injury was accompanied by release of acid phosphatase into the gut lumen, indicating cellular injury.3 Intraperitoneal injection of the nitric oxide (NO) synth~ase inhibitor N0-nitro-L-arginine methyl ester (L-NAME, 2.5-50 mg kg-' twice), prevented the diarrhoea. The dose of L-NAME (50 mg kg-') completely blocked the diarrhoea but increased the release of acid phosphatase and worsened the gross damage. 4 The NO donating compound, isosorbide-5-mononitrate (IMN, 150 mg kg-' twice) reversed the effects of L-NAME (50 mg kg-') on castor oil-induced diarrhoea, gross damage and acid phosphatase release. 5 The apparent dissociation of the diarrhoeal and intestinal mucosal damaging effects of castor oil suggest that NO has a protective effect on the rat duodenal and jejunal mucosa, but that NO mediates, in part, the diarrhoea effect of this laxative.

show abstract

“…The biological effects of the above-listed diversified chemicals have been reviewed.ls. 16 One wonders whether these various detergents could be used as effective absorption enhancers without producing diarrhea. This question has not been thoroughly explored or answered.…”

Section: Ilmr (Min)mentioning

confidence: 99%