Alimentary TractCrucial role for 5-HT in cholera toxin but not Escherichia coli heat-labile enterotoxin-intestinal secretion in rats☆,☆☆
Section snippets
Tissue and luminal release of 5-HT
Experiments were carried out under a Home Office Project Licence. Habituated male adult Wistar rats (180-220 g) were fasted for 18 hours, with free access to water, and anesthetized with sodium pentobarbitone, 60 mg/kg intraperitoneally (IP) plus 10 mg/kg interval injections. Animals were kept at 37°C using a heat pad. After making a midline incision, the whole small intestine was isolated between proximal (5 cm distal to the duodenojejunal flexure) and distal (1-2 cm proximal to the ileocecal
Tissue and luminal release of 5-HT
Both CT and LT induced a gradual change from net intestinal water absorption to secretion over incubation time (Cuzick's test, P < 0.0002). There was no difference in the pattern of onset of secretion between CT and LT (P = 0.13; Figure 1).
Discussion
The role of 5-HT in CT-induced secretion is well established in both animal and human models and is supported by the demonstration of a close temporal relationship between 5-HT release and the onset of CT-induced secretion.12, 13, 14, 35 The degree of 5-HT release that CT induces is substantial because, after 2 hours of incubation, total tissue levels are reduced by 50%. Numerous physicochemical stimuli, including intestinal distention, induce 5-HT release; however, the small intestinal
Acknowledgements
The authors thank Dr. P. Blower of SmithKline Beecham for assistance, Prof. D. Perrett and Dr. I. James of the Department of Metabolism and Endocrinology, St. Bartholomew's Hospital, and Dr. P. Connor of the Digestive Diseases Research Centre, St. Bartholomew's and The Royal London School of Medicine and Dentistry.
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2008, Trends in MicrobiologyCitation Excerpt :This subsequently leads to the exocytosis of serotonin from the enterocromaffin cells, which can act on the enteric nervous system to control muscle contraction or on the enterocytes to induce chloride secretion through the activity of cAMP (Figure 2). CT and the heat-labile toxin (HLT) from enterotoxigenic Escherichia coli are very similar in sequence and structure, but HLT does not act on enterochromaffin cells (Figure 2) [12]. The lack of HLT activity on these cells could provide a rationale for the relatively lower level of diarrhea volume and intensity when compared to CT-based disease [12].
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Address requests for reprints to: James L. Turvill, M.B., Ch.B., M.R.C.P., Digestive Diseases Research Centre, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Turner Street, London, E1 2AD, England. Fax: (44) 171-295-7192.
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Supported by an educational grant from SmithKline Beecham Pharmaceuticals.