A reconsideration of the evidence for Escherichia coli STa (heat stable) enterotoxin-driven fluid secretion: a new view of STa action and a new paradigm for fluid absorption

A review of the evidence for Escherichia coli STa causing fluid secretion in vivo leads to the conclusion that the concept of STa acting through enhanced chloride secretion in order to derange intestinal function is unproven. However, a consistent effect of STa in the small intestine is on Na+/H+ exchange, leading to interruption of luminal acidification. A model for the action of STa, involving inhibition of Na+/H+ exchange, is proposed which explains the ability of STa to reduce absorption in vivo but its inability to cause secretion in vice in contrast to its apparent secretory effect in vitro. The apparent ability to demonstrate secretion in vitro is shown to derive from methodologies which do not involve measurement of mass transport of water but instead, infer it from in vitro and in vivo proxy measurements. The in vitro demonstration of notional secretion after STa exposure can be reconciled with the proposed new model for fluid absorption in that cell swelling is argued to arise as a transient consequence of STa challenge followed by regulatory volume decrease. Evidence for this derangement model is presented in the form of observations derived from acute in vivo physiological studies and clinical studies on patients without the exchanger. This process of appraisal of the evidence for the mechanism of action of STa has led to a new model for fluid absorption. This is based on the formation of hypotonicity at the brush border luminal surface rather than hypertonicity within the lateral spaces as required by the present standing gradient model of fluid absorption. Evidence from the literature is presented for this new paradigm of water absorption, which may only be relevant for small intestine and other tissues that have Na+/H+ exchangers in contact with HCO3--containing solutions but which may also be generalizable to all mammalian absorbing epithelial membranes.