Effect ofEscherichia coliheat-stable enterotoxin, cholera toxin and theophylline on ion transport in porcine colon

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Abstract
The effect of heat-stable enterotoxin (ST) of E. coli, cholera toxin (CT), and theophylline (a phosphodiesterase inhibitor) on ion and water transport was studied with an in vivo isolated loop system of the pig colon. All 3 agents abolished net Na absorption as a result of a decrease in the lumen to blood Na flux alone. With all 3 agents, net Cl absorption was reduced, but not abolished; net HCO3 secretion was elicited. Luminal pCO2 [CO2 pressure] was reduced with CT and theophylline from that observed in normal Ringer alone. Theophylline resulted in a prompt and sustained increase in cAMP and cGMP levels in colonic mucosa studied in vitro. ST selectively elevated cGMP; CT selectively elevated cAMP. These responses paralleled the time course and magnitude of response of the transepithelial electrical potential difference (.psi.LB) measured in vivo. Ion replacement studies in the presence or absence of theophylline showed that in the absence of Na, Cl absorption was slightly reduced and HCO3 secretion was elicited; no further additive effects of theophylline in the absence of luminal Na were observed. In the absence of luminal Cl, net Na absorption was abolished and HCO3 was absorbed; theophylline resulted in significant net Na and HCO3 secretion. Theophylline also increased .psi.LB in the absence of either luminal Na or Cl. In the presence of theophylline or enterotoxin, the coupled Na-H and Cl-HCO3 exchange processes that are normally responsible for at least 1/2 of the net NaCl absorption by this tissue are evidently interrupted. Active HCO3 secretion is observed and Cl absorption under these conditions can be explained as a consequence of .psi.LB. Thus, the colon may participate in the production of diarrhea of enterotoxigenic origin. An important functional role of cyclic nucleotides in controlling the acidity and volume of colonic contents was also suggested.