Modes of Action, Resistance and Toxicity of Insecticides Targeting Nicotinic Acetylcholine Receptors.
BACKGROUND
Nicotinic acetylcholine receptors (nAChRs) of insects play a key role in fast excitatory neurotransmission. Several classes of insecticides target insect nAChRs, which are composed of subunit members of a family of multiple subunit encoding genes. Alternative splicing and RNA A-to-I editing can add further to receptor diversity. Native and recombinant receptors have been explored as sites of insecticide action using radioligands, electrophysiology and site-directed mutagenesis.


METHODS
We have reviewed the properties of native and recombinant insect nAChRs, the challenges of functional recombinant insect nAChR expression, nAChR interactions with ligands acting at orthosteric and allosteric sites and in particular their interactions with insecticides.


RESULTS
Actions on insect nAChRs of cartap, neonicotinoids, spinosyns, sulfoxamines, butenolides and mesoionic insecticides are reviewed and current knowledge of their modes of action are addressed. Mutations that add to our understanding of insecticide action and those leading to resistance are discussed. Co-crystallisation of neonicotinoids with the acetylcholine binding protein (AChBP), a surrogate for the nAChR ligand binding domain, has proved instructive. Toxicity issues relating to insecticides targeting nAChRs are also considered.


CONCLUSIONS
An overview of insecticide classes targeting insect nAChRs has enhanced our understanding of these important receptors and their insecticide binding sites. However, the subunit composition of native nAChRs remains poorly understood and functional expression still presents difficulties. These topics together with improved understanding of the precise sites of insecticide actions on insect nAChRs will be the subject of future research.
Department of Applied Biological Chemistry, Faculty of Agriculture, Kindai University, 3327-204 Nakamachi, Nara 631-8505. Japan.
Makoto
M
Ihara
Centre for Respiratory Biology, UCL Respiratory, Division of Medicine, University College London, Rayne Building, 5 University Street, London WC1E 6JF. United Kingdom.
Steven D
SD
Buckingham
Department of Applied Biological Chemistry, Faculty of Agriculture, Kindai University, 3327-204 Nakamachi, Nara 631-8505. Japan.
Kazuhiko
K
Matsuda
Centre for Respiratory Biology, UCL Respiratory, Division of Medicine, University College London, Rayne Building, 5 University Street London WC1E 6JF. United Kingdom.
David B
DB
Sattelle
D000818:Animals; D004351:Drug Resistance / Q000187:drug effects; D006801:Humans; D007306:Insecticides / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D011744:Pyrimidinones / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D013859:Thiocarbamates / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity
D007306:Insecticides; D018942:Macrolides; D011725:Pyridines; D011744:Pyrimidinones; D011978:Receptors, Nicotinic; D011994:Recombinant Proteins; D013859:Thiocarbamates; C114883:spinosyn A; C000620847:triflumezopyrim; D009538:Nicotine; C032761:carbamothioic acid, S,S'-(2-(dimethylamino)-1,3-propanediyl) ester
Nicotinic acetylcholine receptor; butenolides; insecticide; neonicotinoids; resistance; spinosyns; sulfoximines; toxicity.; triflumezopyrim