Effect of chlorpromazine on ion transport induced by cholera toxin, cyclic AMP and cyclic GMP in isolated mucosa from hen intestine.

The isolated short circuit mucosa of chicken colon was established as an in vitro model for studies of the pathophysiology of diarrhoea and the mechanism of action of antidiarrhoeic drugs. Cholera toxin, 10(-7) M, added to the mucosal aide of the preparation, caused in a delayed reaction a pronounced increase of short circuit current (Isc). Cyclic AMP, which mediates the effect of cholera toxin (when added serosal) induced an immediate rise of Isc. Half maximal reaction was achieved at 3 mM cyclic AMP and maximal at 7 mM. The increase of Isc corresponded to the increase in the flux of chloride from serosa to mucosa. Unlike cyclic AMP, cyclic GMP almost equally stimulated sodium and chloride transport from serosa to mucosa. Unlike cyclic AMP, cyclic GMP almost equally stimulated sodium and chloride transport from serosa to mucosa, while the effect on Isc of the two nucleotides was additive. Chlorpromazine, which effectively reverses diarrhoea in cholera patients, totally normalized Isc after treatment with either cholera toxin, cyclic AMP or cyclic GMP. This reduction was achieved by a specific stimulation of transport of chloride from mucosa to serosa. The effect occurred also without previous treatment of the tissue with secretagogues (cholera toxin, cyclic nucleotides). No change in mucosal resistance was induced by chlorpromazine or cyclic GMP while it was reduced by cyclic AMP.