Comparison of the action of Escherichia coli enterotoxin on the thymocyte adenylate cyclase-cyclic adenosine monophosphate system to that of cholera toxin and prostaglandin E1

Abstract

Mouse thymocytes were used to compare mechanisms by which Vibrio cholerae and heat-labile Escherichia coli enterotoxins activate the adenylate cyclase-cyclic adenosine monophosphate (AMP) system. Both enterotoxins had their time-delayed increase in cyclic AMP neutralized by antisera to V. cholerae or E. coli enterotoxin, blocked by low concentrations of ganglioside G(M1), and destroyed by prior heating. Enterotoxin activation of adenylate cyclase was similarly affected. By contrast, prostaglandin E(1)-mediated increases in cyclic AMP were not affected by specific antitoxins or gangliosides. Combination of maximal stimulatory doses of both enterotoxins did not produce additive increases in cyclic AMP. Wash experiments suggested that both enterotoxins bind rapidly and tightly to thymocytes at 37 C. However, lowering the incubation temperature to 8 C reduced the affinity of E. coli enterotoxin but not cholera toxin for thymocytes. Results suggest that heat-labile E. coli enterotoxin and cholera enterotoxin may activate the same adenylate cyclase enzyme by similar mechanisms.