SEGMENT-SPECIFIC EFFECTS OF THE HEAT-STABLE ENTEROTOXIN OF ESCHERICHIA-COLI ON ELECTROLYTE TRANSPORT IN THE RAT COLON

The heat-stable enterotoxin of E. coli (STa) induced an increase in short-circuit current (Isc) in the rat colon. The maximal increase in Isc was about three times larger in the proximal than the distal colon. The action of STa was mimicked by 8-Br-cyclic GMP. Unidirectional flux measurements revealed that STa decreased Na+ and Cl- absorption in the distal colon, while it decreased Na+ absorption and activated Cl- secretion in the proximal colon. In the distal, but not in the proximal colon, indomethacin inhibited the action of STa and of 8-Br-cyclic GMP. Inhibition by indomethacin could be overcome by addition of prostaglandin E2 or forskolin, but not by addition of a non-hydrolysable analogue of cyclic AMP, suggesting an action of STa on cyclic AMP hydrolysis. Amrinone and trequinsin, two inhibitors of cyclic GMP-inhibited phosphodiesterases, mimicked the action of STa on Isc and inhibited the response to a subsequent administration of the toxin indicating the modulation of a cyclic GMP-inhibited phosphodiesterase by STa in the distal colon. The results give evidence for different intracellular action sites of STa in the two parts of the rat colon.