Effect of theophylline and heat-stable enterotoxin of Escherichia coli on transcellular and paracellular ion movement across isolated porcine colon

Abstract

The effect of theophylline and a heat-stable enterotoxin of Escherichia coli (ST) on ion transport was examined using an in vitro, short-circuited preparation of the porcine colon. Theophylline abolished net Na absorption and elicited net Cl secretion, which quantitatively accounted for the increase in short-circuit current (Isc) observed. In contrast, a maximal dose of ST elicited an Isc response about one-half that of theophylline and only partially reduced the net absorption of Na and Cl. A significant residual ion flux, consistent with HCO3 secretion, was elicited by ST and was sustained after theophylline addition. Ion replacement experiments showed that the Isc and net ion transport response to ST was abolished when either Cl or HCO3 were removed from the bathing solutions. Voltage clamp experiments to evaluate the contribution of the paracellular and transcellular transepithelial pathways from serosa to mucosa showed that approximately one-half of the total serosa-to-mucosa flux (Jsm) of both Na and Cl was through the cells. Theophylline and ST both significantly reduced transcellular JNasm, but did not affect JClsm. Theophylline, but not ST, caused an increase in paracellular conductance of both ions. These results demonstrate significant differences in the effects of ST or theophylline on both transcellular and paracellular ion movement, and suggest that ST induces a Cl-dependent HCO3 secretion which is unobserved under control or theophylline-stimulated conditions. In addition, results are consistent with the operation of a neutral NaCl secretory process which is normally masked by the greater net rates of the neutral Na and Cl absorptive mechanisms. Thus, both ST and theophylline appear to reduce or abolished the neutral processes and convert the neutral secretory process into an electrogenic one. This latter effect could be explained simply by an increase in the anion conductance of the mucosal membranes.