The 2-nitroimino-imidazolidine and related moieties are structural features of neonicotinoid insecticides acting on nicotinic acetylcholine receptors (nicotinic AChRs). To evaluate these moieties in neonicotinoid interactions with nicotinic AChR α subunits, the actions of imidacloprid and related compounds on the chicken α7, α4β2 and Drosophila melanogaster-chicken hybrid (SADβ2 and ALSβ2) receptors expressed in Xenopus laevis oocytes were studied by voltage-clamp electrophysiology. Imidacloprid and nitenpyram were partial agonists and a nitromethylene analog of imidacloprid (CH-IMI) was a full agonist of the α7 receptor, whereas their agonist actions on the α4β2 receptor were very weak, contrasting with full agonist actions of DN-IMI, a desnitro derivative of imidacloprid. The neonicotinoids and DN-IMI were either full or partial agonists of the SADβ2 receptors. Nitenpyram and DN-IMI were partial agonists of the ALSβ2 receptor, whereas imidacloprid and CH-IMI scarcely activated the ALSβ2 receptor. Imidacloprid and CH-IMI in fact suppressed ACh-induced responses of the ALSβ2 receptor, whereas imidacloprid potentiated and CH-IMI suppressed ACh-induced responses of the α4β2 receptor. These results suggest that interactions with α subunits of the 2-nitroimino-imidazolidine moiety of imidacloprid play a role in determining not only agonist and antagonist actions on all four receptors, but also the potentiation of ACh-induced responses of the α4β2 receptor. © 2003 Elsevier Science Ltd. All rights reserved.
- Chicken α4β2 nicotinic receptor
- Chicken α7 nicotinic receptor
- Drosophila ALS chicken β2 hybrid nicotinic receptor
- Drosophila SAD chicken β2 hybrid nicotinic receptor
- Nicotinic acetylcholine receptor