Comparative effects of structurally related cyclodiene pesticides on ATPases

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Abstract
Comparative effects of aldrin, dieldrin, endrin, isodrin and telodrin, on different ATPase activities in beef heart mitochondrial and rat brain synaptosomal fractions were determined in vitro. Beef heart mitochondrial fractions were prepared by the conventional centrifugation method and the rat brain synaptosomes were prepared by Ficoll-sucrose gradient centrifugation method. Na+–K+-ATPase, oligomycin-sensitive and -insensitive Mg2+-ATPases, and K+-paranitrophenylphosphatase were determined in rat brain synaptosomes. In beef heart mitochondria, only the Mg2+-ATPase activities were determined. Concentration response curves were determined by assaying the enzyme activities in the absence and presence of 10–120 μM concentrations of each test chemical. Beef heart mitochondrial (oligomycin-sensitive) Mg2+-ATPase activity was inhibited by all five chemicals at all the concentrations tested. Aldrin and telodrin were the most potent inhibitors with an IC50 of 40 and 80 μM, respectively. About 30% was observed with dieldrin, endrin and isodrin, and the inhibition was not concentration-dependent. Oligomycin-insensitive Mg2+-ATPase was not significantly inhibited by any chemical except aldrin. Rat brain synaptosomal ATPases were also sensitive to these compounds. Aldrin and telodrin were more effective than other compounds. A 50% inhibition of oligomycin-sensitive Mg2+-ATPase activity was obtained at 80 μM of aldrin and telodrin, Na+–K+-ATPase and oligomycin-insensitive Mg2+-ATPase activities showed a maximum inhibition of 40% at the highest concentration tested for aldrin and telodrin. K+-paranitrophenylphosphatase was not inhibited significantly by any compound tested. These results suggest that ATPase system in rat heart and CNS may be selectively inhibited by aldrin and telodrin, but not by their structural analogs.