title: Blocking actions of alkylene-tethered bis-neonicotinoids on nicotinic acetylcholine receptors expressed by terminal abdominal ganglion neurons of Periplaneta americana.
abstract: Neonicotinoid insecticides target nicotinic acetylcholine receptors (nAChRs), which, in both vertebrates and invertebrates, mediate fast-acting synaptic neurotransmission in the nervous system. Recently, Kagabu et al. synthesized bis-neonicotinoids. The neural activities of bis-neonicotinoids have been evaluated on the central nerve cord of American cockroaches. However, the action of bis-neonicotinoids on nAChRs expressed by dissociated insect neurons has not yet been studied. Thus, the actions of several alkylene-tethered bis-neonicotinoids on the terminal abdominal ganglion neurons of the American cockroach, Periplaneta americana, were investigated using whole-cell patch-clamp electrophysiology. All of the ligands tested did not induce membrane currents, but reduced the responses to ACh when bath applied prior to co-application with ACh. Of the compounds tested, HK-13, which possesses two imidacloprid units linked with a hexamethylene bridge, had the highest antagonist potency. The antagonist action was reduced, not only by elongating, but also by shortening the linker.
authors.affiliation: Department of Applied Biological Chemistry, School of Agriculture, Kinki University, Nakamachi 3327-204, Nara 631-8505, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ihara
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Chiharu
authors.initials: C
authors.lastname: Ishida
authors.forename: Shinzo
authors.initials: S
authors.lastname: Kagabu
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Matsuda
mesh_terms: D000691:Anabasine / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions / Q000502:physiology; D017952:Ganglia, Invertebrate / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D007306:Insecticides / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000737:chemistry / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010526:Periplaneta / Q000166:cytology / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology
chemical_list: D007306:Insecticides; D008024:Ligands; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000691:Anabasine