Inhibition of adenylate cyclase and ATPase activities from rat liver plasma membrane by hexachlorophene.

Adenylate cyclase activity from a rat liver plasma membrane preparation purified according to Neville's procedure was inhibited in vitro by low concentrations (1 μM to 0.1 mM) of hexachlorophene. Complete inhibition was obtained with 1 mM hexachlorophene. Similar effects were observed whether the activity was assayed in the presence of 10 μM GTP. 0.1 μm glucagon. 10 mM NaF or without any addition. The effect of hexachlorophene was not due to inhibition of the regenerating system present in the incubation medium, since the effect of the drug was preserved in its absence. The inhibition brought about by hexachlorophene was not reversed by increasing the concentration of the substrate ATP-Mg. The inhibition was immediate and irreversible spontaneously: it was not affected by the simultaneous addition of 2-mercaptoethanol. Hexachlorophene inhibited also the “total” Mg²⁺-ATPase, as well as its Na⁺, K⁺-dependent fraction. These results suggest that the interaction of hexachlorophene with the plasma membrane, as reflected in the inhibition of two major enzymes activities, might play a key role in the toxicity of the drug.