Abstract：
:Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels which mediate fast cholinergic synaptic transmission in insect and vertebrate nervous systems. A point mutation Y151S had been identified in Nilaparvata lugens (brown planthopper) that is associated with target-site resistance to neonicotinoid insecticides. Methionine (M151) is found in the Caenorhabditis elegans alpha subunit acr18 at the corresponding site to Y151 in Nlalpha1. Here, the Y151M mutation was introduced into Nlalpha1 and co-expressed with rat beta2 in Xenopus oocytes. The influence of the Y151M mutation on the affinity and efficacy of acetylcholine and imidacloprid on hybrid nAChRs Nla1/beta2 was examined by radioligand binding and electrophysiology methods. Imidacloprid bound with Nlalpha1(Y151M)/beta2 with high affinity, although this was lower than that of Nlalpha1/beta2. However, imidacloprid did not show agonist actions on Nlalpha1(Y151M)/beta2, although the quite small responses to imidacloprid at high concentrations (0.5-1.0 mM) were detected in some (but not all) oocytes expressing Nlalpha1(Y151M/beta2. Further study demonstrated that imidacloprid acted as an antagonist on Nlalpha1(Y151M)/beta2, which blocked responses to acetylcholine on Nlalpha1(Y151M)/beta2 with a pIC50 of 5.14 +/- 0.06. Nlalpha1(Y151M)/beta2 nAChRs block by imidacloprid was slowly reversible. This is the first time a point mutation in loop B of insect nAChR alpha subunits has been identified that changes the mode of interaction between neonicotinoid insecticides and insect nAChRs.
journal_name
Neurosci Lettjournal_title
Neuroscience lettersauthors
Zhang Y,Liu S,Gu J,Song F,Yao X,Liu Zdoi
10.1016/j.neulet.2008.09.039subject
Has Abstractpub_date
2008-12-03 00:00:00pages
97-100issue
2-3eissn
0304-3940issn
1872-7972pii
S0304-3940(08)01291-3journal_volume
446pub_type
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