Activation and Modulation of Human alpha 4 beta 2 Nicotinic Acetylcholine Receptors by the Neonicotinoids Clothianidin and Imidacloprid

作者：Li Ping; Ann Jason; Akk Gustav^*

来源：Journal of Neuroscience Research, 2011, 89(8): 1295-1301.

DOI：10.1002/jnr.22644

• nicotinic receptor
• neonicotinoid
• insecticide

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 alpha 4 beta 2 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 alpha 4 beta 2 receptor is 18 mu M. 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 (alpha 4)(2)(beta 2)(3) receptors significantly more strongly inhibited than the (alpha 4)(3)(beta 2)(2) receptors.

• 出版日期2011-8