Effect of toxaphene on the binding of 3H-labeled ouabain and dopamine to rat brain synaptosomes.
The effects of toxaphene, a chlorinated hydrocarbon pesticide, on the binding of ouabain and dopamine to rat brain synaptosomes enriched with Na+-K+ ATPase were investigated. For in vitro assessment of the effects of toxaphene, the synaptosomes prepared from normal rats were used. For in vivo effects the rats were fed on 0, 50, 100, 150 and 200 ppm toxaphene mixed in their daily ration for 8 weeks. At the end of treatment the rats were killed and synaptosomes were prepared. Toxaphene inhibited Na+-K+ and Mg2+ ATPases of synaptosomes in vitro and the inhibition was significant and concentration-dependent. The IC50 values were about 30 and 12 microM toxaphene for Na+-K+ and Mg2+ ATPases, respectively. However, much higher concentrations of toxaphene were required to inhibit the binding of [3H]ouabain and [3H]dopamine to synaptosomes. A 50% inhibition of ouabain and dopamine binding was obtained at 150 and 200 microM of toxaphene. The enzyme activities of synaptosomes in toxaphene-pretreated rats were decreased significantly. However, a dose-dependent decrease was not observed. The rats receiving dosages of 100 ppm and above showed a 30-40% decrease in enzyme activities. The binding of ouabain and dopamine to synaptosomes of toxaphene-pretreated rats showed no significant changes as compared to controls. The present in vitro results suggest that toxaphene may be an effective inhibitor of ATPases with substantial effects on the binding of ouabain and dopamine to rat brain synaptosomes. However, data obtained through in vivo studies do not support this contention. The reason for this discrepancy may be that the toxaphene is being rapidly metabolized or might not have reached the site of action.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D017301:Ca(2+) Mg(2+)-ATPase; D004298:Dopamine / Q000378:metabolism*; D007306:Insecticides / Q000494:pharmacology*; D008297:Male; D010042:Ouabain / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013574:Synaptosomes / Q000201:enzymology / Q000378:metabolism*; D014112:Toxaphene / Q000494:pharmacology*
D007306:Insecticides; D010042:Ouabain; D014112:Toxaphene; D000251:Adenosine Triphosphatases; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine