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Neonicotinoid insecticides differently modulate acetycholine-induced currents on mammalian ?7 nicotinic acetylcholine receptors.

ABSTRACT: BACKGROUND AND PURPOSE:Neonicotinoid insecticides are described as poor agonists of mammalian nicotinic ACh receptors. In this paper, we show that their effects on mammalian nicotinic receptors differ between compounds. EXPERIMENTAL APPROACH:Two-electrode voltage-clamp electrophysiology was used to characterize the pharmacology of three neonicotinoid insecticides on nicotinic ?7 receptors expressed in Xenopus oocytes. Single and combined application of clothianidin, acetamiprid and thiamethoxam were tested. RESULTS:Two neonicotinoid insecticides, clothianidin and acetamiprid, were partial agonists of mammalian neuronal ?7 nicotinic receptors, whereas another neonicotinoid insecticide, thiamethoxam, which is converted to clothianidin in insect and plant tissues, had no effect. Pretreatment with clothianidin and acetamiprid (10 ?M) ACh significantly enhanced the subsequent currents evoked by ACh (100 ?M ) whereas pretreatment with thiamethoxam (10 ?M) reduced ACh-induced current amplitudes.A combination of the three neonicotinoids decreased the ACh-evoked currents. CONCLUSIONS AND IMPLICATIONS:The present findings suggest that neonicotinoid insecticides differ markedly in their direct effects on mammalian ?7 nicotinic ACh receptors and can also modulate ACh-induced currents. Furthermore, our data indicate a previously unknown modulation of mammalian ?7 nicotinic receptors by a combination of clothianidin, acetamiprid and thiamethoxam. LINKED ARTICLES:This article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc.

SUBMITTER: Cartereau A

PROVIDER: S-EPMC5978969 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Neonicotinoid insecticides differently modulate acetycholine-induced currents on mammalian α7 nicotinic acetylcholine receptors.

Cartereau Alison A Martin Carine C Thany Steeve H SH

British journal of pharmacology 20171006 11

<h4>Background and purpose</h4>Neonicotinoid insecticides are described as poor agonists of mammalian nicotinic ACh receptors. In this paper, we show that their effects on mammalian nicotinic receptors differ between compounds.<h4>Experimental approach</h4>Two-electrode voltage-clamp electrophysiology was used to characterize the pharmacology of three neonicotinoid insecticides on nicotinic α7 receptors expressed in Xenopus oocytes. Single and combined application of clothianidin, acetamiprid an ...[more]

PMID: 28853147

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Project description:Myzus persicae is a globally important aphid pest with a history of developing resistance to insecticides. Unusually, neonicotinoids have remained highly effective as control agents despite nearly two decades of steadily increasing use. In this study, a clone of M. persicae collected from southern France was found, for the first time, to exhibit sufficiently strong resistance to result in loss of the field effectiveness of neonicotinoids.Bioassays, metabolism and gene expression studies implied the presence of two resistance mechanisms in the resistant clone, one based on enhanced detoxification by cytochrome P450 monooxygenases, and another unaffected by a synergist that inhibits detoxifying enzymes. Binding of radiolabeled imidacloprid (a neonicotinoid) to whole body membrane preparations showed that the high affinity [3H]-imidacloprid binding site present in susceptible M. persicae is lost in the resistant clone and the remaining lower affinity site is altered compared to susceptible clones. This confers a significant overall reduction in binding affinity to the neonicotinoid target: the nicotinic acetylcholine receptor (nAChR). Comparison of the nucleotide sequence of six nAChR subunit (Mp?1-5 and Mp?1) genes from resistant and susceptible aphid clones revealed a single point mutation in the loop D region of the nAChR ?1 subunit of the resistant clone, causing an arginine to threonine substitution (R81T).Previous studies have shown that the amino acid at this position within loop D is a key determinant of neonicotinoid binding to nAChRs and this amino acid change confers a vertebrate-like character to the insect nAChR receptor and results in reduced sensitivity to neonicotinoids. The discovery of the mutation at this position and its association with the reduced affinity of the nAChR for imidacloprid is the first example of field-evolved target-site resistance to neonicotinoid insecticides and also provides further validation of exisiting models of neonicotinoid binding and selectivity for insect nAChRs.

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Neonicotinoid insecticides differently modulate acetycholine-induced currents on mammalian ?7 nicotinic acetylcholine receptors.

Publications

Neonicotinoid insecticides differently modulate acetycholine-induced currents on mammalian α7 nicotinic acetylcholine receptors.

Similar Datasets

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