EFFECTS OF THE ALPHA-SUBUNIT ON IMIDACLOPRID SENSITIVITY OF RECOMBINANT NICOTINIC ACETYLCHOLINE-RECEPTORS

1 Imidacloprid is a new insecticide with selective toxicity for insect s over vertebrates. Recombinant (alpha 4 beta 2) chicken neuronal nico tinic acetylcholine receptors (AChRs) and a hybrid nicotinic AChR form ed by co-expression of a Drosophila melanogaster neuronal alpha subuni t (SAD) with the chicken beta 2 subunit were heterologously expressed in Xenopus oocytes by nuclear injection of cDNAs. The agonist actions of imidacloprid and other nicotinic AChR ligands ((+)-epibatidine, (-) -nicotine and acetylcholine) were compared on both recombinant nicotin ic AChRs by use of two-electrode, voltage-clamp electrophysiology. 2 I midacloprid alone of the 4 agonists behaved as a partial agonist on th e alpha 4 beta 2 receptor: (+)-epibatidine, (-)-nicotine and acetylcho line were all full, or near full, agonists. Imidacloprid was also a pa rtial agonist of the hybrid Drosophila SAD chicken beta 2 receptor, as was (-)-nicotine, whereas (+)-epibatidine and acetylcholine were full agonists. 3 The EC50 of imidacloprid was decreased by replacing the c hicken alpha 4 subunit with the Drosophila SAD alpha subunit. This alp ha subunit substitution also resulted in an increase in the EC50 for ( +)-epibatidine, (-)-nicotine and acetylcholine. Thus, the Drosophila ( SAD) alpha subunit contributes to the greater apparent affinity of imi dacloprid for recombinant insect:vertebrate nicotinic AChRs. 4 Imidacl oprid acted as a weak antagonist of ACh-mediated responses mediated by SAD beta 2 hybrid receptors and as a weak potentiator of ACh response s mediated by alpha 4 beta 2 receptors, This suggests that imidaclopri d has complex effects upon these recombinant receptors, determined at least in part by the alpha subunit.