COMPARATIVE EFFECTS OF CHLORDECONE AND MIREX ON RAT CARDIAC ATPASES AND BINDING OF H-3-LABELED CATECHOLAMINES

Abstract

The effects of chlordecone and mirex [pesticides] on the rat myocardial ATPases and binding of 3H-dopamine and 3H-norepinephrine to the NAK[semipurified membrane]-fraction were determined both by in vitro and in vivo treatment. The in vitro data showed that chlordecone significantly inhibited mitochondrial Mg2+ ATPase and Na+-K+ ATPase in a concentration dependent manner with median inhibitory doses values of 5 .times. 10-8 and 2 .times. 10-6 M, respectively. Mirex, a close structural analog of chlordecone did not inhibit mitochondrial Mg2+ ATPase but inhibited about 15% of N+-K+ ATPase activity. Rats treated with symptomatogenic doses of chlordecone showed a marked and significant decrease of myocardial Na+-K+ ATPase and the residual Mg2+ ATPase activities. The decrease in the enzyme activities was dose dependent and significant. Mirex-treated rats showed a slight decrease in the myocardial Na+-K+ ATPase. The potency of chlordecone to inhibit the ATPase system was parallel to its ability to decrease the dopamine and norepinephrine binding of the myocardial NAK-fraction. Preincubation of the NAK-fraction with various concentrations of chlordecone resulted in a decreased binding of dopamine and norepinephrine. The decrease was significant and concentration dependent. Similar findings were observed in rats pretreated with chlordecone. Mirex did not show any effect, either in vitro or in vivo treatment, on the binding of dopamine or norepinephrine to the myocardial NAK-fraction. Chlordecone may be altering the Na pump activity by inhibiting both ATP hydrolysis and ATP synthesis and thus reducing other cellular events such as catecholamine uptake.