Intestinal adenyl-cyclase activity in canine cholera: correlation with fluid accumulation.

Abstract

Recent evidence suggests that the diarrheal effect of cholera enterotoxin is mediated by stimulation of intestinal adenyl cyclase and increased formation of intracellular adenosine 3' , 5' -cyclic monophosphate (cyclic AMP). This study demonstrates the stimulation of adenyl cyclase in canine jejunal mucosa by cholera toxin during experimental cholera. Percentage increase of basal adenyl-cyclase activity correlates in time course and magnitude with simultaneously measured changes of net water and sodium fluxes. Onset of enzyme activation and change of net water and sodium fluxes occur simultaneously between 30 and 60 min. Maximal changes in activity of the enzyme and net movement of water and sodium also coincide at 150 and 180 min. By 48 hr, the restoration of normal fluxes is accompanied by the return of enzymatic activity to baseline value. Regression analysis shows a linear correlation between the percentage of adenyl-cyclase stimulation and the magnitude of changes of net water and sodium flux. These data strongly support the hypothesis that adenyl cyclase is the mediator of the accumulation of intestinal fluid in cholera.