Additive effects of ileal secretagogues in the rat

Although clinical diarrhea is often caused by more than one enteropathogen, it is not known whether secretagogues have additive effects on secretion. This question was examined in anesthetized, ventilated rats by exposing the ileum to secretory agents with different mechanisms of action. Four hours after inoculation of ileal loops with either cholera toxin or saline, transport was measured during perfusion with Ringer's solution, with Ringer's solution containing Escherichia coli heat-stable enterotoxin or mannitol, or with Ringer's solution containing both heat-stable enterotoxin and mannitol. We found that heat-stable enterotoxin caused similar decrements in water absorption in loops exposed to Ringer's solution, hypertonic mannitol, cholera toxin, and cholera toxin plus mannitol. By contrast, the decrement in water transport caused by hypertonic mannitol was inversely related to the level of ongoing water transport. In addition, the electrolyte transport changes caused by each enterotoxin were preserved despite the presence of other secretory agents. These data suggest that the transport effects of secretagogues with different mechanisms of action are additive in the ileum. However, the absolute decrements in water absorption may be independent of (heat-stable enterotoxin and cholera toxin) or dependent on (hypertonic mannitol) the ongoing level of water transport.