Activation and modulation of human α4β2 nicotinic acetylcholine receptors by the neonicotinoids clothianidin and imidacloprid
- 28 April 2011
- journal article
- research article
- Published by Wiley in Journal of Neuroscience Research
- Vol. 89 (8), 1295-1301
- https://doi.org/10.1002/jnr.22644
Abstract
Neonicotinoids are synthetic, nicotine‐derived insecticides used for agricultural and household pest control. Though highly effective at activating insect nicotinic receptors, many neonicotinoids are also capable of directly activating and/or modulating the activation of vertebrate nicotinic receptors. In this study, we have investigated the actions of the neonicotinoids clothianidin (CTD) and imidacloprid (IMI) on human neuronal α4β2 nicotinic acetylcholine receptors. The data demonstrate that the compounds are weak agonists of the human receptors with relative peak currents of 1–4% of the response to 1 mM acetylcholine (ACh). Coapplication of IMI strongly inhibited currents elicited by ACh. From Schild plot analysis, we estimate that the affinity of IMI for the human α4β2 receptor is 18 μM. The application of low concentrations of CTD potentiated responses to low concentrations of ACh, suggesting that receptors occupied by one ACh and one CTD molecule have a higher gating efficacy than receptors with one ACh bound. Interestingly, subunit stoichiometry affected inhibition by CTD, with (α4)2(β2)3 receptors significantly more strongly inhibited than the (α4)3(β2)2 receptors.Keywords
This publication has 28 references indexed in Scilit:
- The neuronal nicotinic α4β2 receptor has a high maximal probability of being openBritish Journal of Pharmacology, 2010
- Pentameric concatenated (α4)2(β2)3 and (α4)3(β2)2 nicotinic acetylcholine receptors: subunit arrangement determines functional expressionBritish Journal of Pharmacology, 2009
- Combined roles of loops C and D in the interactions of a neonicotinoid insecticide imidacloprid with the α4β2 nicotinic acetylcholine receptorNeuropharmacology, 2009
- Potentiating and blocking actions of neonicotinoids on the response to acetylcholine of the neuronal .ALPHA.4.BETA.2 nicotinic acetylcholine receptorJournal of Pesticide Science, 2008
- α4β2 Nicotinic Receptors with High and Low Acetylcholine Sensitivity: Pharmacology, Stoichiometry, and Sensitivity to Long-Term Exposure to NicotineMolecular Pharmacology, 2006
- Human Exposure to Imidacloprid from Dogs Treated with Advantage®Toxicology Mechanisms and Methods, 2005
- Diverse actions of neonicotinoids on chicken α7, α4β2 and Drosophila–chicken SADβ2 and ALSβ2 hybrid nicotinic acetylcholine receptors expressed in Xenopus laevis oocytesNeuropharmacology, 2003
- Correlations of the electrophysiological activity of neonicotinoids with their binding and insecticidal activitiesPest Management Science, 2003
- Alternate Stoichiometries of α4β2 Nicotinic Acetylcholine ReceptorsMolecular Pharmacology, 2003
- Effects of the α subunit on imidacloprid sensitivity of recombinant nicotinic acetylcholine receptorsBritish Journal of Pharmacology, 1998