Inhibition of cholera toxin activation of the adenylate cyclase system in intact HeLa cells

Abstract

Cholera toxin treatment activates the adenylate cyclase in intact HeLa cells. However, pretreatment of the cells with chemicals known to inhibit receptor internalization and lysosomal processing blocks the toxin activation. The agents found to inhibit the effect of cholera toxin include methylamine, ammonium chloride, chloroquine and dansylcadaverine. These chemicals did not affect either the binding of )125I)-cholera toxin to HeLa cells nor the ability of A1 peptide to activate the adenylate cyclase in plasma membrane preparations. We conclude that these chemicals act on the processing of the toxin subsequent to its binding and that internalization and lysosomal processing mediate the release of the active fragment from cholera toxin, which activates the adenylate cyclase system.