Effect of selected insecticides on rat brain synaptosomal adenylate cyclase and phosphodiesterase.
Previous reports from our laboratory and others clearly indicated that organochlorine insecticides such as chlordecone and DDT are potent inhibitors of ATPases involved in active ion transport. The present studies were initiated to study the effect of plictran, chlordecone, toxaphene, aldrin, dieldrin, endrin, isodrin, and telodrin on enzymes involved in cyclic AMP metabolism. Rat brain synaptosomes were prepared by Ficoll-sucrose gradient centrifugation method. Adenylate cyclase activity, which is involved in anabolism of cAMP, was determined using the radioactive method by measuring [32P]cAMP formed during hydrolysis of [32P]ATP. Phosphodiesterase activity, which is involved in the catabolism of cAMP, was estimated by measuring [3H]adenosine formed using [3H]cAMP as a substrate. Synaptosomal adenylate cyclase activity was inhibited significantly by plictran with an IC50 of 25 microM, and a maximum inhibition of 30% was observed with 50 microM chlordecone. Toxaphene, aldrin, dieldrin, endrin, isodrin, and telodrin did not affect the adenylate cyclase activity. Similarly, none of the insecticides studied inhibit the activity levels of synaptosomal phosphodiesterase. The significant inhibition of adenylate cyclase observed with plictran might be due to the tin component, since several heavy metals affect cAMP metabolism. The lack of inhibition of adenylate cyclase and phosphodiesterase with other compounds tested clearly supports our postulation that these organochlorine insecticides exert their neurotoxic action by the selective inhibition of ATPases in synaptosomes.
Kodavanti
P R
PR
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson.
Mehrotra
B D
BD
Chetty
S C
SC
Desaiah
D
D
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D006843:Hydrocarbons, Chlorinated; D066298:In Vitro Techniques; D007306:Insecticides / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012969:Sodium Fluoride / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects* / Q000201:enzymology
D006843:Hydrocarbons, Chlorinated; D007306:Insecticides; D012969:Sodium Fluoride; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases