J Pharm Pharmacol. 1983 Mar;35(3):152-6.
Influence of prostacyclin and indomethacin on castor oil-induced gastrointestinal effects in rats.
Vischer P, Casals-Stenzel J.
The effects of castor oil, alone, as well as in combination with PGI2 and indomethacin on gastrointestinal functions have been examined in rats. Oral administration of the oil to fasted rats induced severe diarrhoea, with increased intestinal motility and fluid volume. Pretreatment with PGI2 (s.c.) inhibited the effect of the oil on intestinal fluid accumulation and decreased intestinal motility below control values, but only delayed the occurrence of mucoid diarrhoea. Indomethacin (i.p.) reduced the accumulation in intestinal fluid after castor oil administration to a much smaller extent (47%) than PGI2 and depressed the increased intestinal motility to control values. In contrast to PGI2, indomethacin inhibited the occurrence of diarrhoea after administration of castor oil. The present results do not definitely confirm the general opinion that the diarrhoeal action of laxative agents is due only to an altered intestinal electrolyte and water transport or an increase of intestinal motility.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6132971&dopt=Abstract constipation laxative
Scand J Gastroenterol Suppl. 1982;71:111-24.
Ultrastructural changes in the gut autonomic nervous system following laxative abuse and in other conditions.
Riemann JF, Schmidt H.
Electronmicroscopical studies have been carried out on colonic biopsies from patients with long-term laxative abuse, amyloidosis, diabetic autonomic neuropathy or chronic inflammatory bowel disease. The results of these investigations indicate that submucosal nerve fibres are damaged to an extent dependent upon the intensity of the toxic agent. The main pathological features range from distension or ballooning of axons, reduction of nerve-specific cell structures and increase in lysosomes to a total degeneration of whole nerve fibres. While the degenerative process is uniform, differentiation between disease states can be made on the basis of specific additional lesions such as the presence of typical amyloid fibrils, diabetic microangiopathy or the inflammatory process in inflammatory bowel disease. No changes were found in Whipple's disease or gluten-sensitive enteropathy. It is concluded that the structural alterations may provide a morphological explanation for the disturbances in gut motility, as an intact intramural nervous system is a necessary prerequisite for the regular coordination of normal peristalsis.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6176011&dopt=Abstract constipation laxative
Biochim Biophys Acta. 1981 Nov 6;648(2):215-24.
Effects of secretagogues on the K+ permeability of mucosal and serosal borders of rabbit colonic mucosa.
Moreto M, Planas JM, Naftalin RJ.
(1) K+ efflux rates from the mucosal and serosal surfaces of sheets of rabbit colonic mucosa have been determined by measuring net K+ loss into K+-free Ringer solution bathing each side of the tissue. (2) Initially, there is a high rate of K+ loss from the tissue, this falls to a lower steady-state rate after 20 min. Loss of K+ from the tissue into the serosal bath is 6-8 fold faster than loss to the mucosal bath. (3) A number of intestinal secretagogues, e.g. theophylline, cyclic AMP, carbachol, ionophore A23187, as well as the laxative bisacodyl, raise the K+ efflux rate across the mucosal border by 200-300%. In the case of K+ efflux induced by carbachol the effect is shown to be dependent on raised levels of intracellular Ca2+. Ca2+-calmodulin complex does not appear to be be involved in activation of K+ efflux across the mucosal border. (4) Amiloride does not block mucosal K+ efflux, but tetraethyl-ammonium does inhibit K+ efflux across the mucosal border, induced by either bisacodyl or raised intracellular Ca2+. (5) The results suggest that laxatives may increase the rate of K+ secretion into the colonic lumen by raising the K+ permeability of the mucosal border.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6272851&dopt=Abstract constipation laxative
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