J Pharmacol Exp Ther. 1975 Feb;192(2):458-67.
Inhibitory actions of laxatives on motility and water and electrolyte transport in the gastrointestinal tract.
Stewart JJ, Gaginella TS, Olsen WA, Bass P.
Castor oil and magnesium sulfate were studied for their effects on gastrointestinal contractile activity in vivo. Ricinoleic acid, the active ingredient in castor oil, magnesium sulfate and mannitol were studied and compared for their effects on net water and electrolyte absorption in vitro. Extraluminal strain gauge transducers were implanted in dogs and used to monitor the circular smooth muscle activity of the antrum, duodenum, ileum and colon after water, castor oil or a 30 percent solution of magnesium sulfate. Substances were tested during the interdigestive (fasted) and digestive (fed) states. Decreases in total activity were found for both cathartics in the antrum and ileum. Further analysis revealed that decreases in the ileum occurred primarily by a decrease in contractile rate, whereas antral decreases could be attributed primarily to a decrease in force per contraction. Proximal colonic activity tended to decrease after laxatives and feeding. The effects of ricinoleic acid, isotonic and hypertonic solutions of magnesium sulfate and mannitol on net water and electrolyte absorption were tested on everted segments of hamster jejunum. Sodium ricinoleate (2.0 mM) reduced net water transport by 48 percent (P smaller than .01). Magnesium sulfate, like mannitol, only reduced net water absorption when present as a component of a hypertonic mucosal solution. The results suggest that both inhibition of water absorption and reduced circular smooth muscle activity may be important factors in castor oil- and magnesium sulfate-induced catharsis.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1117429&dopt=Abstract constipation laxative
Farmaco [Sci]. 1975 Feb;30(2):147-58.
[Transport and mode of action of sennosides]
[Article in Italian]
Dobbs HE, Lane AC, Macfarlane IR.
Prior to attempting to develop a new laxative, pharmacodynamic studies were conducted on the individual active constituents of senna. Sennoside A, sennoside B and rhein were injected intravenously and were introduced into the isolated stomach, small bowel and large bowel of the anaesthetised pig. Blood, urine and bile, collected over 6 hours, were assayed by a novel fluorometric technique. Recoveries and measured oil water partition coefficients indicate that the sennosides are virtually non-absorbed in the stomach and small bowel. Following administrations outside the large bowel, anthracene derivative concentrations in the lumen and wall of the colon were below the limits of detection. Thus, a transport theory involving absorption and resecretion of sennosides into the large bowel is discounted. The results support a mode of action involving direct transport through the alimentary canal to the large bowel where micro-organism break the sugar-anthracene bonds. Derivatives of the liberated lipophilic aglycones are absorbed into the wall of the colon and stimulate the nerve plexuses thereby leading to defaecation. The "colon-specific" mode of action of the natural anthrone glycosides appears to be an ideal method of stimulating bowel action.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1123037&dopt=Abstract constipation laxative
Gut. 1975 May;16(5):372-8.
Differential measurement of small and large bowel transit times in constipation and diarrhoea: A new approach.
Differential measurements of small and large bowel transit times were performed in 13 subjects iwth a radiotelemetering pressure-sensitive capsule incorporating less than 10mugCi of 51-Cr. Six patients had constipation. The other seven patients had diarrhoea due to the irritable bowel syndrome (3), following vagotomy and pyloroplasty (3), or due to laxative abuse (1). This new method enables the gastric, small intestinal, and colonic transit times to be measured differentially in the same subject. The capsule can be localized in the gut lumen by reference to the characteristic pressure pattern and in relation to bony landmarks by the radioactive marker as frequently as desired without recourse to radiographs. The results show that gastric emptying and small intestinal transit did not differ in constipation and diarrhoea. By contrast the mean colonic transit was significantly faster (P smaller than 0.01) in diarrhoea whatever the cause (17.5 plus or minus 4.1 hours) than in constipation (118 plus or minus 4.1 hours).
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1140635&dopt=Abstract constipation laxative
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