Mechanism of inhibition of rat brain (Na + K)-adenosine triphosphatase by 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (DDT).

Inhibition of an (Na + K)-ATPase preparation from rat brain by DDT was five times as effective when the insecticide was particulate than when solubilized by the surfactant, Corexit 7664. The surfactant reduced binding of DDT to the membranes by about 5 fold. Inhibition correlated with the amount of DDT bound rather than with its concentration or physical state. In the absence of the surfactant, maximal inhibition and binding occurred when the membranes contained about 350 pmoles/μg of protein, an amount equal to 12 per cent of the protein content of the membranes. At low concentrations most of the DDT present is bound by the membranes, hence its effect decreases as membrane concentration increases. The kinetics of inhibition of the (Na + K)-ATPase by DDT, allenthrin and DDE were examined by varying the concentrations of inhibitor, Na⁺, or K⁺, while holding the concentration of the others constant. Inhibition by all of these compounds was potentiated by increased K⁺, and the increment in the inhibition caused by K⁺ was reversible by increased Na⁺ concentrations. Hence the effectiveness of DDT is dependent on the membrane concentration and the relative concentrations of Na⁺ and K⁺. The concentration of DDT required for maximal inhibition suggests that the inhibition is not caused by binding to a specific site on the enzyme, but is the result of indirect alterations of the membrane which interfere with allosteric transitions of the (Na + K)-ATPase mediated by Na⁺ and K⁺.