CYP6D1 PROTECTS THORACIC GANGLIA OF HOUSEFLIES FROM THE NEUROTOXIC INSECTICIDE CYPERMETHRIN

CYP6D1 is a housefly cytochrome P450 known to metabolize neurotoxic py rethroid insecticides. To determine if the nervous system was capable of metabolizing pyrethroids, we examined CYP6D1-mediated in vitro meta bolism in thoracic ganglia from pyrethroid-resistant (LPR) and -suscep tible (CS) strains of housefly. SDS-PAGE/immunoblotting revealed that CYP6D1 was expressed in all tagmata and in thoracic ganglia of both st rains, but in all cases the levels of CYP6D1 were higher in the LPR st rain. Using a CYP6D1-specific antiserum, we fouled CYP6D1 to be the ma jor, and possibly the only, P450 isozyme involved in cypermethrin meta bolism in thoracic ganglia homogenates. Additionally, thoracic ganglia homogenates from LPR houseflies metabolize more cypermethrin than pre parations from susceptible flies. This metabolism was inhibited by pip eronyl butoxide and a CYP6D1-specific antibody. Our results indicate t hat thoracic ganglia of LPR houseflies are protected from the neurotox in cypermethrin by virtue of the higher levels of CYP6D1 compared to t he susceptible houseflies. This P450-mediated detoxification of an ins ecticide at the level of the target tissue helps to explain the high l evels of resistance to pyrethroids in the LPR strain. (C) 1998 Wiley-L iss, Inc.