Evidence for p-glycoprotein modification of insecticide toxicity in mosquitoes of the Culex pipiens complex.
Pesticide resistance has parallels with multi-drug resistance syndrome of tumours in clinical medicine, which has been linked to an ATP-dependent pump, p-glycoprotein (P-gp). P-gps pump drugs out of the cell, thereby reducing cellular concentrations of the chemical. P-gps have been found in several invertebrate species and have been shown to provide a defence against environmental xenobiotics, including pesticides. This study used a model cell culture system to investigate the interaction of pesticides with P-gp. Ivermectin and endosulfan were shown to be strong inhibitors of dye transport out of cells, which is a standard measure of P-gp modulation. We then investigated the action of a P-gp inhibitor, verapamil (calcium channel blocker), on insecticide toxicity to fourth-instar mosquito larvae of the Culex pipiens L. complex (Diptera: Culicidae). Verapamil increased toxicity to examples of three insecticide classes (cypermethrin, endosulfan, ivermectin), but not to chlorpyrifos (organophosphate). The discovery of a novel protective mechanism in mosquitoes, with a wide substrate range, has implications for the control of important pest and vector species.
Division of Zoology, School of Animal & Microbial Sciences, The University of Reading, UK.
D S
DS
Buss
A R
AR
McCaffery
A
A
Callaghan
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003465:Culex / Q000187:drug effects / Q000254:growth & development*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D007300:Insect Control / Q000379:methods; D007303:Insect Vectors / Q000187:drug effects / Q000254:growth & development; D007306:Insecticides / Q000494:pharmacology*; D007559:Ivermectin / Q000494:pharmacology; D008297:Male; D008954:Models, Biological; D009943:Organophosphorus Compounds; D014700:Verapamil / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002121:Calcium Channel Blockers; D007306:Insecticides; D009943:Organophosphorus Compounds; D007559:Ivermectin; D014700:Verapamil