Effects of cholera toxin on adenylate cyclase. Studies with guanylylimidodiphosphate

Similarities exist between the properties of adenylate cyclase after stimulation by cholera toxin and after stimulation by guanylylimidodiphosphate (Gpp-(NH)p). Thus a strong stimulation is achieved by both agents, the stimulation is essentially irreversible, the action of certain hormones is enhanced and the enzyme can be solublized with Lubrol PX in the activated state. Because of these similarities the interaction of cholera toxin and Gpp(NH)p on adenylate cyclase was examined. It was found that prior activation of rat liver adenylate cyclase by cholera toxin in vivo, or by cholera toxin and NAD in homogenates, blocked the stimulatory effect of Gpp(NH)p. Furthermore under conditions in which the effect of Gpp(NH)p was less than that of cholera toxin, inhibition of stimulation by cholera toxin was seen. Stimulation of adenylate cyclase by maximal concentrations of Gpp(NH)p, but not by submaximal concentrations, blocked the stimulatory effect of cholera toxin. The mutant interference of the actions of these two agents suggests a common target in the regulatory mechanism of the adenylate cyclase complex.