The Effect of Chlorpromazine on the Function of Colonic and Ileal Mucosa in the Anaesthetized Rat

1 The effect of chlorpromazine (Cpz) on the net fluxes of water and sodium in the ileum and colon has been studied in the anaesthetized rat. 2 Under control conditions both the ileum and colon absorbed water and sodium. Cpz (100 mumol/kg, s.c.) had no significant effect on these basal rates of absorption. 3 Intestinal secretion was stimulated by a combination of intra-arterial prostaglandin E1 (PGE1; 10 nmol kg-1 min-1) and intraluminal theophylline (25 mM). A marked potentiation occurred between PGE1 and theophylline in the stimulation of colonic and ileal secretion. 4 In the ileum, a dose-related inhibition of the PGE 1/theophylline-induced changes in the net fluxes of water and sodium was produced by Cpz (0.1 to 100 mumol/kg, s.c.). Under these conditions the inhibition of the secretagogue-induced changes was significant using Cpz at 1 mumol/kg (s.c.) and a dose of Cpz of 100 mumol/kg (s.c.) returned the net fluxes of both water and sodium to basal levels. 5 In the colon, Cpz, at doses of 0.1 and 1 mumol/kg subcutaneously did not inhibit the PGE1/theophylline-induced changes in the net fluxes of water and sodium, and, in contrast with the ileum, significant changes were only obtained with Cpz at 10 mumol/kg. Increasing the dose of Cpz to 100 mumol/kg further inhibited the net flux of sodium, but not that of water in the colon, and in each case the secretagogue-induced changes were not returned to basal levels.