Stimulation of Adenylate Cyclase by Vibrio cholerae Toxin and Its Active Subunit

The mechanism by which Vibrio cholerae toxin and its active subunit A stimulate adenylate cyclase of rat liver plasma membrane after in vivo or in vitro exposure was investigated. Stimulation of adenylate cyclase was more efficient with cholera toxin than with subunit A in whole animals and in "soluble" preparations of adenylate cyclase. Toxin-stimulated plasma membrane adenylate cyclase activity persisted after solubilization from the membrane by detergent, while subunit A stimulation was destroyed by detergent treatment. Detergent-free "soluble" enzyme could be stimulated in vitro by cholera toxin, but such stimulation by subunit A was very weak. Binding studies with iodotoxin or iodosubunit A confirmed that the interaction of toxin with adenylate cyclase in "soluble" preparations could be the result of specific binding to the enzyme. The uncertainty as to whether GMl ganglioside (galactosyl-N-acetylgalactosaminyl [sialosyl] lactosyl ceramide; GGnSLC) is present in these fractions limited the interpretation of the data on binding. A biological modification of subunit A prior to the activation of adenylate cyclase is inferred from these data.