Effects of chlorpromazine on fluid transport across the intestinal mucosa of the rat.

The effect of chlorpromazine (CPZ) on net fluid transport in the small intestine of the rat was studied, using a ligated loop model. Given intramuscularly at 5 mg/kg, CPZ induced a 50% increase of net fluid absorption in jejunum, but had no effect in ileum. Similarly, the drug decreased net fluid accumulation induced by dibutyryl-cyclic AMP in jejunum, but did not influence net fluid accumulation in ileum. In contrast, net fluid accumulation induced by cholera toxin was decreased by CPZ in both jejunum and ileum. Inhibition of cyclic AMP (cAMP)-which probably mediates the hypersecretion by the toxin-was also noted. These results suggest that CPZ reverses fluid transport during cholera in two ways: by a cAMP-independent enhancement of fluid absorption in jejunum and by inhibition of the toxin-induced cAMP-production in jejunum as well as ileum. Each of these processes may be independently affected by pharmacological substances and subjected to neural and hormonal regulation.