Effect of chlorpromazine on intestinal secretion mediated by Escherichia coli heat-stable enterotoxin and 8-Br-cyclic GMP in infant mice

Abstract

Subcutaneously administered chlorpromazine reduced intestinal fluid accumulation induced by Escherichia coli heat-stable enterotoxin in infant mice. The antisecretory effect of chlorpromazine, although dose related, was, even with high doses, less than that observed with respect to cholera toxin. Whereas 100 μg chlorpromazine abolished cholera toxin-induced intestinal secretion almost completely, 500 μg chlorpromazine (equivalent to 200 μg/g body wt) lowered secretion induced by heat-stable enterotoxin by only 41%. The effect of chlorpromazine on intestinal secretion was quantitatively similar regardless of whether heat-stable enterotoxin or the cyclic GMP analogue, 8-Br-cyclic GMP, was the secretagogue. This finding, which suggested that the inhibitory effect of chlorpromazine on heat-stable enterotoxin was independant of guanylate cyclase, was confirmed by assaying this enzyme in intestinal homogenates from mice that had been inoculated with chlorpromazine, and also in experiments in which chlorpromazine was added to guanylate cyclase assay mixtures in vitro. Caution is advised before chlorpromazine is routinely adopted for the treatment of all syndromes of watery diarrhea.