K. Matsuda et al., EFFECTS OF THE ALPHA-SUBUNIT ON IMIDACLOPRID SENSITIVITY OF RECOMBINANT NICOTINIC ACETYLCHOLINE-RECEPTORS, British Journal of Pharmacology, 123(3), 1998, pp. 518-524
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.