Effects of chlordecone and its structural analogs on p-nitrophenyl phosphatase.
The effects of chlordecone, mirex, and four photoderivatives of mirex on K+-stimulated p-nitrophenyl phosphatase (KPNPPase) in rat brain synaptosomes were determined. Additionally, the effect of chlordecone on the substrate and K+ activation kinetics and the inhibition of KPNPPase at 17, 27, and 37 degrees C were determined. The sensitivity of KPNPPase to various chemicals was highly variable. Chlordecone was the most effective inhibitor with an IC50 of 6.2 X 10(-6)M. All other chemicals showed a maximum inhibition of 20% at 20 muM concentration. The order of inhibition at 20 muM concentration was chlordecone (100%) greater than 8-monohydro mirex (20%) greater than 2,8-dihydromirex (10%) greater than mirex (10%) greater than 10-monohydro mirex (9%) greater than 5,10-dihydro mirex (2%). Double reciprocal plots of the data obtained on the effect of chlordecone on the substrate and K+ activation kinetics showed that the Vmax and Km were decreased with respect to paranitrophenyl phosphate, while it was competitive inhibition with respect to K+ activation. Chlordecone inhibited KPNPPase more at 37 degrees C than at 27 degrees C and 17 degrees C suggesting a positive temperature effect. These results suggest that chlordecone is the most effective inhibitor among its structural analogs tested on KPNPPase in rat brain synaptosomes.
D009597:4-Nitrophenylphosphatase / Q000037:antagonists & inhibitors*; D000818:Animals; D001921:Brain / Q000201:enzymology; D007631:Chlordecone / Q000031:analogs & derivatives / Q000494:pharmacology*; D007306:Insecticides / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000201:enzymology; D013696:Temperature
D007306:Insecticides; D010744:Phosphoric Monoester Hydrolases; D009597:4-Nitrophenylphosphatase; D007631:Chlordecone