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Role of loop D of the α7 nicotinic acetylcholine receptor in its interaction with the insecticide imidacloprid and related neonicotinoids
Author(s) -
Matsuda Kazuhiko,
Shimomura Masaru,
Kondo Yumi,
Ihara Makoto,
Hashigami Kaori,
Yoshida Naofumi,
Raymond Valérie,
Mongan Nigel P,
Freeman John C,
Komai Koichiro,
Sattelle David B
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703374
Subject(s) - epibatidine , imidacloprid , nicotinic agonist , acetylcholine receptor , nicotine , xenopus , chemistry , pharmacology , nicotinic acetylcholine receptor , nicotinic antagonist , acetylcholine , agonist , receptor , biology , biochemistry , neuroscience , pesticide , gene , agronomy
The nitroguanidine insecticide imidacloprid along with a second generation of related compounds including nitenpyram, all nicotinic acetylcholine (ACh) receptor ligands, are used increasingly in many countries. Site‐directed mutagenesis and heterologous expression in Xenopus laevis oocytes have been deployed to investigate mutants (G189D and G189E) of the chicken α7 homomer‐forming nicotinic receptor subunit which are predicted to enhance the negative charge at the negative subsite (loop D) of the ACh binding site.Xenopus oocytes expressing wild‐type α7 nicotinic receptors respond to imidacloprid with rapid inward currents. Imidacloprid and nitenpyram are partial agonists, whereas ACh, (−)‐nicotine and (+)‐epibatidine are full agonists. Compared to wild‐type α7, the mutant G189D and G189E receptors are much less sensitive to the insecticides, whereas their sensitivity to (−)‐nicotine, ACh and (+)‐epibatidine is only slightly reduced. In contrast, G189N and G189Q mutants are sensitive not only to ACh, (−)‐nicotine and (+)‐epibatidine, but also to the two insecticides. Thus reduction of the insecticide‐sensitivity by the mutations G189D and G189E are attributed to an increase in negativity of loop D. Desnitro‐imidacloprid (DN‐IMI), an imidacloprid derivative lacking the nitro group is a potent agonist on the G189D and G189E mutants suggesting an important role of loop D in nicotinic receptor interactions with the nitro group of nitroguanidine insecticides.British Journal of Pharmacology (2000) 130 , 981–986; doi: 10.1038/sj.bjp.0703374