Effect of cycloheximide on intestinal secretion induced by hypertonic glucose.

Since intestinal fluid production in experimental cholera can be limited by cycloheximide, an inhibitor of protein synthesis, the same agent was used to determine whether there are similar mechanisms for fluid production in response to an osmotic gradient. Intestinal fluid production was measured by perfusion of paired rabbit jejunal loops (10 cm) in vivo, in controls, and in animals receiving 20 mg/kg intravenous cycloheximide one hour before perfusion. In each animal one loop was perfused with isotonic Ringer's lactate and the other with a hypertonic glucose-Ringer's lactate solution, 563 mOsm/litre. In control animals mean fluid production in the hypertonic loop was seven times that in the isotonic loop. Cycloheximide decreased the fluid response to the hypertonic stimulus by one half (p < 0.001). In a separate measurement of bidirectional sodium fluxes, using sodium(22), it was shown that the decreased net sodium movement into the lumen observed after cycloheximide was the result of decreased flux from blood to lumen. The major histological alteration after cycloheximide was on the crypt epithelial cells with sparing of villus crests. Glucose absorption was unaffected. These data parallel the observed effect of cycloheximide on cholera exotoxin induced secretion, suggesting that a process requiring continued protein synthesis is also necessary for the intestinal fluid response to an osmotic gradient.