Diarrhoeal disease through enterocyte secretion: a doctrine untroubled by proof.
For almost 40 years, one of the principal causes of diarrhoeal disease has been thought to be fluid secretion emanating from the epithelial cells of the small and large intestine. Given the extremely large fluid losses seen in cholera, where secretion can be up to several litres per day, this seems a plausible hypothesis. The enterocyte (epithelial cell) secretion hypothesis rapidly displaced all other alternatives, such as vasodilatation coupled with enhanced paracellular permeability. An essential mechanism underlying enterocyte secretion has always been assumed to be electrogenic chloride secretion, leading to a localized osmotic imbalance at the mucosal surface of the enterocytes that causes fluid entry into the lumen by osmosis. The chloride secretion basis for enterotoxin-deranged secretion is assumed to be measurable by changes in electrical currents and by altered transport of chloride ion. These can be detected after the small intestine is exposed to a heat-stable enterotoxin (STa) produced by Escherichia coli. However, in vivo, when the recovered volume technique is used, STa is found not to be secretory. The heat-stable enterotoxin is therefore a test case toxin, because the complex techniques used to demonstrate enterocyte secretion after STa exposure show apparent secretion, while the simplest technique based on fluid recovery and genuinely measuring the mass transport of fluid does not. This review scrutinizes the nature of the evidence put forward for enterocyte secretion and reaches the conclusion that there is no evidence for it. Debilitating secretion undoubtedly does take place in severe diarrhoeal disease, but secretion from enterocytes is unlikely to be the cause.
Division of Neuroscience and Molecular Pharmacology, Faculty of Biomedical & Life Sciences, Glasgow University, Glasgow G12 8QQ, UK. m.lucas@bio.gla.ac.uk
Michael L
ML
Lucas
D000818:Animals; D001427:Bacterial Toxins; D002712:Chlorides / Q000378:metabolism; D002771:Cholera / Q000503:physiopathology*; D003967:Diarrhea / Q000503:physiopathology*; D020895:Enterocytes / Q000378:metabolism*; D004768:Enterotoxins / Q000502:physiology; D029968:Escherichia coli Proteins; D006801:Humans
D001427:Bacterial Toxins; D002712:Chlorides; D004768:Enterotoxins; D029968:Escherichia coli Proteins; C034151:heat stable toxin (E coli)