Comparison of the Effects of E. coli STa with E. coli LT, Clostridium difficile Toxin A and Osmotic Burdens on Small Intestinal Fluid Transport: Additional Proof that STa is Not a Secretory Enterotoxin

Abstract

Using a recirculation procedure to perfuse anaesthetised rat jejunum, E. coli STa enterotoxin can be shown to inhibit net fluid absorption profoundly, while not causing net fluid secretion, provided fluid measurement is by mass or volume. This observation contradicts many reports of STa causing secretion, implying that the recovered volume technique in the anaesthetised animal over a period of some hours cannot detect secretion because of conjectured or unspecified flaws. Experiments are presented here confirming the viability of the perfusion protocol used in this laboratory but also demonstrate that if secretion were to be occurring, the recovered volume protocol would detect it. It will only return a negative finding, if secretion does not occur. To this end, the effect of two secretory toxins on intestinal fluid movement in a closed loop preparation were studied to demonstrate that the anaesthetic, intestinal preparation or perfusion duration did not hinder the demonstration of net secretion when the intestine was exposed to E. coli LT and C. difficile toxin A.. It is evident that STa itself only reduces net absorption but can appear to be secretory if driving forces such as luminal osmotic pressure or capillary hydrostatic pressure through vasodilatation are introduced, as was likely to have occurred with pithing and theophylline. The recognition that STa is a non-secretory enterotoxin necessarily falsifies several alternative methods that claim to demonstrate secretion. Since STa is not secretory many other substances identified by these methods need also not be secretory and alternative explanations must be found to explain their action. The importance of recognising that action on the small intestine cannot be attributed to a secretory mechanism within the enterocyte adds further weight to the concept that where net secretion does occur, the likely mechanism for it is a combination of increased vasodilatation together with increased hydraulic conductivity.