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  • Title: Desensitization of nicotinic acetylcholine receptors in central nervous system neurons of the stick insect (Carausius morosus) by imidacloprid and sulfoximine insecticides.
    Author: Oliveira EE, Schleicher S, Büschges A, Schmidt J, Kloppenburg P, Salgado VL.
    Journal: Insect Biochem Mol Biol; 2011 Nov; 41(11):872-80. PubMed ID: 21878389.
    Abstract:
    Imidacloprid, sulfoxaflor and two experimental sulfoximine insecticides caused generally depressive symptoms in stick insects, characterized by stillness and weakness, while also variably inducing postural changes such as persistent ovipositor opening, leg flexion or extension and abdomen bending that could indicate excitation of certain neural circuits. We examined the same compounds on nicotinic acetylcholine receptors in stick insect neurons, which have previously been shown to desensitize in the presence of ACh. Brief U-tube application of 10(-4) M solutions of insecticides for 1 s evoked currents that were much smaller than ACh-evoked currents, and depressed subsequent ACh-evoked currents for several minutes, indicating that the compounds are low-efficacy partial agonists that potently desensitize the receptors. Much lower concentrations of insecticides applied in the bath for longer periods did not activate currents, but inhibited ACh-evoked currents via desensitization of the receptors. Previously described fast- and slowly-desensitizing nACh currents, I(ACh1) and I(ACh2) respectively, were each found to consist of two components with differing sensitivities to the insecticides. Imidacloprid applied in the bath desensitized high-sensitivity components, I(ACh1H) and I(ACh2H) with IC(50)s of 0.18 and 0.13 pM, respectively. It desensitized the low-sensitivity slowly desensitizing component, I(ACh2L), with an IC(50) of 2.6 nM, while a component of the fast-desensitizing current, I(ACh1L), was least sensitive, with an IC(50) of 81 nM I(ACh1L) appeared to be insensitive to the three sulfoximines tested, whereas all three sulfoximines potently desensitized I(ACh1H) and both slowly desensitizing components, with IC(50)s between 2 and 7 nM. We conclude that selective desensitization of certain nAChR subtypes can account for the insecticidal actions of imidacloprid and sulfoximines in stick insects.
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