title: Diverse actions of neonicotinoids on chicken alpha7, alpha4beta2 and Drosophila-chicken SADbeta2 and ALSbeta2 hybrid nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes.
abstract: The 2-nitroimino-imidazolidine and related moieties are structural features of neonicotinoid insecticides acting on nicotinic acetylcholine receptors (nicotinic AChRs). To evaluate these moieties in neonicotinoid interactions with nicotinic AChR alpha subunits, the actions of imidacloprid and related compounds on the chicken alpha7, alpha4beta2 and Drosophila melanogaster-chicken hybrid (SADbeta2 and ALSbeta2) receptors expressed in Xenopus laevis oocytes were studied by voltage-clamp electrophysiology. Imidacloprid and nitenpyram were partial agonists and a nitromethylene analog of imidacloprid (CH-IMI) was a full agonist of the alpha7 receptor, whereas their agonist actions on the alpha4beta2 receptor were very weak, contrasting with full agonist actions of DN-IMI, a desnitro derivative of imidacloprid. The neonicotinoids and DN-IMI were either full or partial agonists of the SADbeta2 receptors. Nitenpyram and DN-IMI were partial agonists of the ALSbeta2 receptor, whereas imidacloprid and CH-IMI scarcely activated the ALSbeta2 receptor. Imidacloprid and CH-IMI in fact suppressed ACh-induced responses of the ALSbeta2 receptor, whereas imidacloprid potentiated and CH-IMI suppressed ACh-induced responses of the alpha4beta2 receptor. These results suggest that interactions with alpha subunits of the 2-nitroimino-imidazolidine moiety of imidacloprid play a role in determining not only agonist and antagonist actions on all four receptors, but also the potentiation of ACh-induced responses of the alpha4beta2 receptor.
authors.affiliation: Department of Agricultural Chemistry, Faculty of Agriculture, Kinki University, 3327-204 Nakamachi, Nara 631-8505, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ihara
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Matsuda
authors.forename: Maiko
authors.initials: M
authors.lastname: Otake
authors.forename: Morihiko
authors.initials: M
authors.lastname: Kuwamura
authors.forename: Masaru
authors.initials: M
authors.lastname: Shimomura
authors.forename: Koichiro
authors.initials: K
authors.lastname: Komai
authors.forename: Miki
authors.initials: M
authors.lastname: Akamatsu
authors.forename: Valérie
authors.initials: V
authors.lastname: Raymond
authors.forename: David B
authors.initials: DB
authors.lastname: Sattelle
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D029721:Drosophila Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D000073943:Neonicotinoids; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D009574:Nitro Compounds; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D014982:Xenopus laevis; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D029721:Drosophila Proteins; D006146:Guanidines; D007093:Imidazoles; D008024:Ligands; D000073943:Neonicotinoids; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D009574:Nitro Compounds; D021122:Protein Subunits; D011725:Pyridines; D011978:Receptors, Nicotinic; D011993:Recombinant Fusion Proteins; D064569:alpha7 Nicotinic Acetylcholine Receptor; C114279:nAChRalpha1 protein, Drosophila; C403531:nicotinic receptor alpha4beta2; C464843:nitenpyram; C082359:imidacloprid