title: Unique biochemical and molecular biological mechanism of synergistic actions of formamidine compounds on selected pyrethroid and neonicotinoid insecticides on the fourth instar larvae of Aedes aegypti (Diptera: Culicidae).
abstract: We recently reported that formamidine pesticides such as amitraz and chlordimeform effectively synergize toxic actions of certain pyrethroid and neonicotinoid insecticides in some insect species on the 4th instar larvae of Aedes aegypti. Here we studied the biochemical basis of the synergistic actions of the formamidines in amplifying the toxicity of neonicotinoids and pyrethroids such as dinotefuran and thiamethoxam, as well as deltamethrin-fenvalerate type of pyrethroids. We tested the hypothesis that their synergistic actions are mediated by the octopamine receptor, and that the major consequence of octopamine receptor activation is induction of trehalase to increase glucose levels in the hemolymph. The results show that formamidines cause a significant up-regulation of the octopamine receptor and trehalase mRNA expressions. Furthermore, formamidines significantly elevate levels of free glucose when co-treated with dinotefuran, deltamethrin and fenvalerate, but not with permethrin or fenitrothion, which showed no synergistic toxic effects with formamidines. These results support the conclusion that the main mode of synergism is based on the ability to activate the octopamine receptor, which is particularly effective with insecticides causing hyperexcitation-induced glucose release and consequently leading to quick energy exhaustion.
authors.affiliation: Plant Protection Department, Faculty of Agriculture, Assiut University, Assiut 71526, Egypt; Center for Health and the Environment, University of California Davis, CA 95616, USA.
authors.forename: Mohamed Ahmed Ibrahim
authors.initials: MA
authors.lastname: Ahmed
authors.affiliation: Center for Health and the Environment, University of California Davis, CA 95616, USA; Department of Environmental Toxicology, University of California Davis, CA 95616, USA. Electronic address: cfvogel@ucdavis.edu.
authors.forename: Christoph F A
authors.initials: CF
authors.lastname: Vogel
authors.affiliation: Center for Health and the Environment, University of California Davis, CA 95616, USA; Department of Environmental Toxicology, University of California Davis, CA 95616, USA.
authors.forename: Fumio
authors.initials: F
authors.lastname: Matsumura
mesh_terms: D000330:Aedes / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D000818:Animals; D002742:Chlorphenamidine / Q000494:pharmacology*; D004331:Drosophila melanogaster / Q000187:drug effects / Q000254:growth & development; D005260:Female; D005278:Fenitrothion / Q000633:toxicity; D005947:Glucose / Q000378:metabolism; D006146:Guanidines / Q000633:toxicity; D007093:Imidazoles / Q000633:toxicity; D007306:Insecticides / Q000633:toxicity*; D007814:Larva / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008297:Male; D000073943:Neonicotinoids; D009570:Nitriles / Q000633:toxicity; D009574:Nitro Compounds / Q000633:toxicity; D010078:Oxazines / Q000633:toxicity; D026023:Permethrin / Q000633:toxicity; D010574:Pesticide Synergists / Q000494:pharmacology*; D011722:Pyrethrins / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D017982:Receptors, Biogenic Amine / Q000819:agonists* / Q000235:genetics; D000077922:Thiamethoxam; D013844:Thiazoles / Q000633:toxicity; D014052:Toluidines / Q000494:pharmacology*; D014198:Trehalase / Q000235:genetics; D015854:Up-Regulation
chemical_list: D006146:Guanidines; D007093:Imidazoles; D007306:Insecticides; D000073943:Neonicotinoids; D009570:Nitriles; D009574:Nitro Compounds; D010078:Oxazines; D010574:Pesticide Synergists; D011722:Pyrethrins; D012333:RNA, Messenger; D017982:Receptors, Biogenic Amine; D013844:Thiazoles; D014052:Toluidines; C027604:norsynephrine receptor; C465368:dinotefuran; C017180:decamethrin; C014983:amitraz; C082359:imidacloprid; D026023:Permethrin; D000077922:Thiamethoxam; D014198:Trehalase; D002742:Chlorphenamidine; D005947:Glucose; D005278:Fenitrothion
keywords: Aedes aegypti; Formamidines; Octopamine receptor; Trehalose; qRT-PCR