title: Binding of imidacloprid, thiamethoxam and N-desmethylthiamethoxam to nicotinic receptors of Myzus persicae: pharmacological profiling using neonicotinoids, natural agonists and antagonists.
abstract: BACKGROUND
  The increasing structural diversity of the neonicotinoid class of insecticides presently used in crop protection calls for a more detailed analysis of their mode of action at their cellular targets, the nicotinic acetylcholine receptors.
  
  
  RESULTS
  Comparative radioligand binding studies using membranes of Myzus persicae (Sulzer) and representatives of the chloropyridyl subclass (imidacloprid), the chlorothiazolyl subclass (thiamethoxam), the tetrahydrofuranyl subclass (dinotefuran), as well as the novel sulfoximine type (sulfoxaflor), which is not a neonicotinoid, reveal significant differences in the number of binding sites, the displacing potencies and the mode of binding interference. Furthermore, the mode of interaction of [3H]thiamethoxam and the nicotinic antagonists methyllycaconitine and dihydro-β-erythroidine is unique, with Hill values of >1, clearly different to the values of around unity for [3H]imidacloprid and [3H]N-desmethylthiamethoxam. The interaction of [3H]N-desmethylthiamethoxam with the agonist (-)nicotine is also characterised by a Hill value of >1.
  
  
  CONCLUSIONS
  There is no single conserved site or mode of binding of neonicotinoids and related nicotinic ligands to their target receptor, but a variety of binding pockets depending on the combination of receptor subunits, the receptor subtype, its functional state, as well as the structural flexibility of both the binding pockets and the ligands. © 2016 Society of Chemical Industry.
authors: Institute of General Zoology and Endocrinology, Ulm University, Ulm, Germany. hartmut.kayser@uni-ulm.de.
authors: Hartmut
authors: H
authors: Kayser
authors: Institute of General Zoology and Endocrinology, Ulm University, Ulm, Germany.
authors: Katrin
authors: K
authors: Lehmann
authors: Syngenta Crop Protection AG, Basel, Switzerland.
authors: Marilyne
authors: M
authors: Gomes
authors: Institute of General Zoology and Endocrinology, Ulm University, Ulm, Germany.
authors: Wolfgang
authors: W
authors: Schleicher
authors: Institute of General Zoology and Endocrinology, Ulm University, Ulm, Germany.
authors: Karin
authors: K
authors: Dotzauer
authors: Institute of General Zoology and Endocrinology, Ulm University, Ulm, Germany.
authors: Margarethe
authors: M
authors: Moron
authors: Syngenta Crop Protection AG, Basel, Switzerland.
authors: Peter
authors: P
authors: Maienfisch
mesh_terms: D000818:Animals; D001042:Aphids / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D019476:Insect Proteins / Q000235:genetics* / Q000378:metabolism; D007306:Insecticides / Q000494:pharmacology*; D000073943:Neonicotinoids; D018722:Nicotinic Agonists / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000378:metabolism; D009574:Nitro Compounds / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000235:genetics* / Q000378:metabolism; D000077922:Thiamethoxam; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D006146:Guanidines; D007093:Imidazoles; D019476:Insect Proteins; D007306:Insecticides; D000073943:Neonicotinoids; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D009574:Nitro Compounds; D010078:Oxazines; D011978:Receptors, Nicotinic; D013844:Thiazoles; C480342:clothianidin; C082359:imidacloprid; D000077922:Thiamethoxam
keywords: insect control; insecticides; mode of action; neonicotinoids; nicotinic acetylcholine receptor; radioligand assay