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A, structure of the nicotinic receptor agonist nicotine (upper left) compared with imidacloprid (upper right), clothianidin (lower right), and acetamiprid (lower left). B, comparative electrophysiological and pharmacological properties of nAChR1 and nAChR2 expressed by the cockroach DUM neurons (from Courjaret and Lapied, 2001; Thany et al., 2008).
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Neonicotinoid insecticides act selectively on insect nicotinic acetylcholine receptors (nAChRs). Recent studies revealed that their efficiency was altered by the phosphorylation/dephosphorylation process and the intracellular signaling pathway involved in the regulation of nAChRs. Using whole-cell patch-clamp electrophysiology adapted for dissociat...
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Context 1
... of Nicotine, Imidacloprid, and Acetamiprid on -Bungarotoxin-Insensitive nAChRs Expressed in DUM Neurons. As demonstrated previously, DUM neurons expressed both -bgt-insensitive and "mixed" nAChRs, which were blocked by extracellular application of 0.5 M -bgt ( Lapied et al., 1990;Courjaret and Lapied, 2001) (Fig. 2B). In this condition, pressure ejection application of Nic (10 mM, 100 ms) onto DUM neuron somata evoked a transient inward current (Fig. 3A). As reported previously (Courjaret and Lapied, 2001;Courjaret et al., 2003;Thany et al., 2008), when the peak amplitude of the inward currents was plotted against the steady-state holding ...
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... the inward currents was plotted against the steady-state holding potentials a biphasic aspect was observed (Fig. 3B). The peak amplitude decreased lin- early between 90 and 30 mV and then increased between 30 and 30 mV. This unusual biphasic aspect indicated that Nic acted on two different subtypes of -bgt-insensitive nAChRs, nAChR1 and nAChR2 ( Fig. 2B) (Courjaret and Lapied, 2001;Courjaret et al., 2003: Thany et al., 2008. It is noteworthy that after pressure application of IMI (0.1 mM, 100 ms) we never observed a biphasic current-voltage curve ( Fig. 3C) (Courjaret and Lapied, 2001), whereas ACT (1 mM, 200 ms) induced a similar effect as that of Nic (Fig. 3D). These last results ...
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... from the open to closed state in the pres- ence of agonist. Consequently, an increase in Nic-induced current amplitude indicated that nAChR2 was more open before pressure application of Nic. In contrast, a decrease in the current amplitude suggests that nAChR2 is in a less open conformational state before application of the cholinergic ag- onist (Fig. 2B). Based on these results and to ensure that only ionic current flowing through nAChR2 was recorded with 50 M d-TC bath-applied, the input membrane resistance was measured under current-clamp condition, at a membrane potential of 70 mV, in control and after bath application of Nic (100 M). As illustrated in Fig. 5, C and D, an increase ...
Citations
... Electrophysiological studies performed on cockroach dorsal unpaired median (DUM) neurons, located in the sixth abdominal ganglion, showed that a pressure application of acetamiprid onto isolated DUM neuron somata induced a biphasic dose-response curve. These results demonstrated that it acted as an agonist on both cockroach nicotinic acetylcholine receptor 1 and 2 subtypes, whereas imidacloprid only activated the subtype 1 [19]. At the synaptic level, using the synapse between the cercal afferent giant interneuron and the nerve XI, it was demonstrated that acetamiprid induced a strong dose-dependent increase in the ganglionic depolarisation [18]. ...
... −1 ), clothianidin led to uncoordinated movements, leg shakings, and prostration in intoxicated cockroaches. However, when exposed to thiamethoxam, cockroaches only demonstrated excitatory signs with a characteristic shaking of legs [19]. Moreover, we found that the two major nitroimines (thiamethoxam [20] and clothianidin [21]) decreased cockroach locomotor activity. ...
Toxicological studies have shown that the American cockroach Periplaneta americana (Linnaeus) is a classical model for studying the mode of action of commonly used insecticides. In a previous study, we demonstrated that thiamethoxam and clothianidin decreased locomotor activity in an open-field-like apparatus. Here, we tested the effect of the neonicotinoid acetamiprid when applied orally, topically, or injected into the haemolymph. We found that acetamiprid was also able to impair locomotor activity in the open-field-like apparatus. When treated with acetamiprid, a strong alteration in locomotor activity was observed 1 h, 24 h, and 48 h after haemolymph and topical applications. Oral application induced an impairment of locomotor activity at 24 h and 48 h. A comparison of the present data with our previously published results showed that neonicotinoids were more active when injected into the haemolymph compared to oral and topical applications. These findings increased our understanding of the effect of neonicotinoid insecticides on insect locomotor activity, and demonstrated that the cyano-substituted neonicotinoid, acetamiprid, was able to alter cockroach locomotor activity.
... Electrophysiological studies performed on cockroach dorsal unpaired median (DUM) neurons, located in the sixth abdominal ganglion, showed that a pressure application of acetamiprid onto isolated DUM neuron somata induced a biphasic dose-response curve. These results demonstrated that it acted as an agonist on both cockroach nicotinic acetylcholine receptor 1 and 2 subtypes, whereas imidacloprid only activated the subtype 1 [19]. At the synaptic level, using the synapse between the cercal afferent giant interneuron and the nerve XI, it was demonstrated that acetamiprid induced a strong dose-dependent increase in the ganglionic depolarisation [18]. ...
... -1 ), clothianidin led to uncoordinated movements, leg shakings and prostration in intoxicated cockroaches. However, when exposed to thiamethoxam, cockroaches only demonstrated excitatory signs with characteristic shaking of legs [19]. Moreover, we found that the two major nitro-imines (thiamethoxam [20] and clothianidin [21]) decreased cockroach locomotor activity. ...
Toxicological studies have shown that the cockroach Periplaneta americana is a classical model for studying the mode of action of commonly used insecticides. In a previous study, we demonstrated that thiamethoxam and clothianidin decreased locomotor activity and decreased the locomotor activity in an open-field-like apparatus. Here, we tested the effect of the neonicotinoid acetamiprid when applied orally, topically, or injected into the haemolymph. We found that acetamiprid decreased locomotor activity in the open-field-like apparatus. When treated with acetamiprid, a strong alteration in locomotor activity was observed 1 h, 24 h and 48 h after haemolymph and topical applications. Oral application of acetamiprid demonstrated that it impaired locomotor activity at 24 h and 48 h. A comparison of the present data with our previously published results showed that neonicotinoids were more active when injected into the haemolymph compared to oral and topical applications. These findings increased our understanding of the effect of neonicotinoid insecticides on insect locomotor activity, and demonstrated that the cyano-substituted neonicotinoid, acetamiprid, was able to alter cockroach locomotor activity.
... Moreover, increasing the ejection time of ACh did not induce a semilogarithmic dose-response curve, suggesting the presence of desensitizing currents. Indeed, there is a linear relationship between the pressure ejection time and the molar concentration of the compound applied by the pressure ejection system (Bodereau-Dubois et al., 2012). For cockroach DUM neurons, we found that compounds applied in these conditions induced a semilogarithmic dose-response curve (Bodereau-Dubois et al., 2012;. ...
... Indeed, there is a linear relationship between the pressure ejection time and the molar concentration of the compound applied by the pressure ejection system (Bodereau-Dubois et al., 2012). For cockroach DUM neurons, we found that compounds applied in these conditions induced a semilogarithmic dose-response curve (Bodereau-Dubois et al., 2012;. These results suggested that I. ricinus AChRs expressed in the ~25 and ~ 35 μm cells were strongly desensitized under pulse application of ACh. ...
... For example, in the American cockroach Periplaneta americana, imidacloprid acts as an antagonist of nicotinic receptor 1 (nAChR1) instead of nAChR2 [46][47][48]. In contrast, acetamiprid binds to nAChR2 [49,50]. Acetamiprid is rapidly biotransformed into several compounds such as 6-chloronicotinic acid. ...
Coccinella septempunctata is a nontarget beneficial arthropod and an important aphid predator in agricultural crops. In this study, the toxic effects of the neonicotinoid acetamiprid on C. septempunctata were investigated to determine its applicability and efficacy against the aphid predator. The results of the toxicity test showed that the second instar larvae of C. septempunctata were the most sensitive to acetamiprid. The LC50 values of the 1st, 2nd, 3rd, and 4th instar larvae were 15.767, 9.412, 18.850, and 25.278 mg a.i. L−1, respectively. Compared with that of the control, the predation ability of different larval instars was inhibited by sublethal concentrations of acetamiprid. The results of the predatory function test showed that sublethal concentrations of acetamiprid could reduce the consumption of aphids by fourth instar C. septempunctata larvae over a short duration and significantly inhibited the predatory ability of ladybird larvae. The results of the developmental test showed that sublethal concentration of acetamiprid shortened the growth duration of C. septempunctata larvae. Acetamiprid had considerable adverse effects on the different developmental stages of C. septempunctata. Together, our results provide information for implementation in biological and chemical control strategies for the integrated management of aphids.
... CaM-kinase II (Lavialle-Defaix et al. 2010;Bodereau-Dubois et al. 2012;Calas-List et al. 2013;List et al. 2014;Raymond et al. 2017). De précédentes études réalisées au laboratoire SiFCIR indiquent que chez la blatte P. ...
Les maladies vectorielles sont causées par des agents pathogènes transmis d’un hôte à un autre par un insecte vecteur. Le moyen de lutte le plus efficace contre ces maladies reste à l’heure actuelle l’utilisation de produits phytosanitaires comme les insecticides. Cependant, l’utilisation non raisonnée des insecticides au cours des dernières décennies a conduit à l’apparition de populations d’insectes résistants entrainant une diminution de l’efficacité des traitements insecticides. De plus, les politiques institutionnelles tendent vers une diminution du nombre de substances disponibles. Il devient donc nécessaire de mettre en place de nouvelles stratégies de lutte contre les insectes vecteurs de maladies. Des études chez la blatte Periplaneta americana ont montré que l’activation des récepteurs muscariniques (mAChRs) entrainait l’augmentation du calcium intracellulaire. Cette augmentation de calcium permet d’accroître la sensibilité des cibles aux insecticides. Ainsi, lesmAChRs pourraient jouer un rôle dans les nouvelles stratégies de lutte contre les insectes nuisibles. Nous avons donc entrepris de caractériser les mAChRs chez le moustique Anopheles gambiae, vecteur du paludisme. Trois types de mAChRs ont été mis en évidence : le mAChR-A, deux variants du mAChR-B (mAChR-B1 et mAChR-B2) et le mAChR-C. L’expression du mAChR-A dans un système hétérologue, les cellules Sf9, a permis sa caractérisation fonctionnelle et pharmacologique. Des tests de mesure de l’activité de l’acétylcholinestérase 1 (AChE1) d’An. gambiae dans les cellules Sf9 ont montré que l’activation du mAChR-A module la sensibilité de l’AChE1 au chlorpyrifos-éthyl, un insecticide organophosphoré. L’ensemble des résultats suggère que les mAChRs peuvent être considérés comme des facteurs importants dans le développement de nouvelles stratégies de lutte contre les insectes vecteurs de maladie
... Many calcium-dependent cellular and molecular factors can modulate insecticide efficacy through the activation of specific, complex signaling cascades that trigger phosphorylation/dephosphorylation process. This modulatory effect has been demonstrated in vitro with different classes of conventional insecticides, including phenylpyrazoles, neonicotinoids, pyrethroids, oxadiazines, organophosphates, and carbamates, acting on insect receptors and ion channels, such as voltage-dependent sodium channel channels (NaV), nicotinic acetylcholine receptor (nAChR), gamma-aminobutyric acid receptor (GABAR), and acetylcholinesterase (AChE) [21,24,25,[28][29][30][31][32][33]. These intracellular signal transduction cascades typically amplify the calcium-dependent messages via the stimulation of effector enzymes (e.g., adenylyl cyclase, phospholipase C, guanylate cyclase), which catalyze the production or, in the case of ions, release of the second messengers (e.g., calcium ions, cAMP, cGMP, diacylglycerol, and IP3). ...
Among novel strategies proposed in pest management, synergistic agents are used to improve insecticide efficacy through an elevation of intracellular calcium concentration that activates the calcium-dependent intracellular pathway. This leads to a changed target site conformation and to increased sensitivity to insecticides while reducing their concentrations. Because virus-like particles (VLPs) increase the intracellular calcium concentration, they can be used as a synergistic agent to synergize the effect of insecticides. VLPs are self-assembled viral protein complexes, and by contrast to entomopathogen viruses, they are devoid of genetic material, which makes them non-infectious and safer than viruses. Although VLPs are well-known to be used in human health, we propose in this study the development of a promising strategy based on the use of VLPs as synergistic agents in pest management. This will lead to increased insecticides efficacy while reducing their concentrations.
... (Courjaret et Lapied, 2001;Thany et al., 2007;Stokes et al., 2015;Mannai et al., 2016). Sur les neurones de blatte P. americana, l'activité des nAChRs est aussi régulée par des voies de signalisation calciumdépendantes impliquant l'AMPc, la PKA, le complexe calcium-calmoduline et des isoformes de la CaMKII qui augmentent ou diminuent la sensibilité des nAChRs aux agonistes et aux insecticides néonicotinoïdes (Thany et al., 2007;Bodereau-Dubois et al., 2012;Calas-List et al., 2013;List et al., 2014;Raymond et al., 2017). ...
... Des expériences de docking moléculaire et d'électrophysiologie sur plusieurs espèces d'insectes ont déterminé que certains néonicotinoïdes comme l'imidaclopride sont majoritairement des agonistes partiels des nAChRs d'insectes alors que d'autres comme la clothianidine ou l'acétamépride sont plutôt des agonistes pleins ou même des super-agonistes (Tan et al., 2007;Simon-Delso et al., 2015). Pour rappel, un agoniste partiel peut induire une réponse proportionnelle au nombre de récepteurs occupés mais même en occupant tous les L'affinité de chaque néonicotinoïde est cependant dépendante du sous-type de nAChR concerné, mais aussi de plusieurs facteurs cellulaires comme l'état de phosphorylation du récepteur ainsi que son état conformationnel (Nauen et al., 2001;Brown et al., 2006;Bodereau-Dubois et al., 2012;Taillebois et al., 2018). Il a été montré que l'augmentation de la concentration en AMPc dans le cytoplasme par une adénylate cyclase sensible au complexe calcium-calmoduline active la PKA qui inhibe la réponse des nAChRs de type nAChR1 à l'imidaclopride, un insecticide néonicotinoïde, via des mécanismes de phosphorylation sur des neurones de blattes P. ...
... Il est connu que les nAChRs sont des récepteurs qui peuvent être perméables au calcium (e.g. α7 nAChR) et que leur activité peut être également modulée de manière allostérique par le calcium extracellulaire et/ou intracellulaire (Thany et al., 2007(Thany et al., , 2008Bodereau-Dubois et al., 2012;Calas-List et al., 2013;List et al., 2014;Changeux, 2018). La nicotine, l'agoniste de choix des nAChRs, a aussi été testée sur les neurones isolés de moustiques Kis et AcerKis pour discriminer les différentes populations de nAChRs exprimées. ...
De nos jours, la lutte anti-vectorielle s’appuie principalement sur l’utilisation des insecticides. Cependant, l’apparition de résistances au sein des populations de moustiques réduit l’efficacité de ces molécules. A l’aide d’une approche multidisciplinaire réalisée in vitro sur des neurones isolés de trois souches de moustiques Anopheles gambiae, une souche sensible (Kis) et deux souches résistantes aux insecticides de type organophosphorés/carbamates (AcerKis) et pyréthrinoïdes (KdrKis), il a été possible de montrer pour la première fois qu’il existe des mécanismes de compensation cellulaires et moléculaires associés aux résistances ace-1R sur l’acétylcholinestérase et kdr sur le canal sodium dépendant du potentiel. Ces mécanismes doivent être considérés pour adapter des stratégies de lutte chimique car ils affectent les propriétés électropharmacologiques des récepteurs cholinergiques de type nicotinique. Ils modulent l’effet de l’acétylcholine, le neurotransmetteur endogène, mais aussi de la clothianidine, un insecticide néonicotinoïde agoniste de ces récepteurs. Au contraire, l’effet du triflumézopyrime, un insecticide mésoionique antagoniste compétitif de ces récepteurs ne semble pas affecté par ces mécanismes de compensation. Cette étude a été complétée par des tests toxicologiques comparatifs réalisés in vivo sur les larves de ces trois souches. Les effets de la clothianidine et du triflumézopyrime ont été testés seuls et associés au répulsif IR3535, utilisé comme agent synergisant pour optimiser l’efficacité du traitement. Les deux association sont montré un effet synergique fort, justifiant l’intérêt de les proposer comme nouvelles stratégies de lutte.
... A previous study demonstrated that the nicotine-elicited currents recorded from cockroach Periplaneta americana neurosecretory cells called dorsal unpaired median (DUM) neurons can be modified after a subchronic exposure to a sublethal dose of imidacloprid . DUM neurons which are commonly used as biological models to study the mode of action of insecticides (Pelhate et al., 1990;Stankiewicz et al., 2012) are known to express two distinct α-bungarotoxin-insensitive nAChR subtypes named nAChR1 and nAChR2 (Courjaret and Lapied, 2001;Bodereau-Dubois et al., 2012;Sun et al., 2017). These nAChRs can be distinguished according to their pharmacological profiles and to their subunit composition. ...
... The authors suggested that intracellular signaling calcium-dependent pathways could regulate nAChR2 function. Indeed, different cellular and molecular factors including calciumdependent signaling pathways modulate the sensitivity of nAChR2 to neonicotinoid insecticides (Bodereau-Dubois et al., 2012;Calas-List et al., 2013;Mannai et al., 2016). However, it wasn't demonstrated if the nAChR2 subtypes from exposed cockroaches are made of the same nAChR subunits as that those from non-exposed cockroaches. ...
Neonicotinoids are the most important class of insecticides used as pest management tools during several decades. Exposition of insect to sublethal dose of insecticide induces physiological and cellular changes that could contribute to the adaptation of the insects in order to loss their sensitivity to insecticides. The aim of our study is to demonstrate that a subchronic exposure to a sublethal dose of a neonicotinoid imidacloprid is sufficient to induce molecular changes leading to a loss of imidacloprid sensitivity. We report that in the cockroach, Periplaneta americana, subchronic exposure to a sublethal dose of imidacloprid induced weak changes in detoxification enzyme activity and a significant decrease of the nicotinic acetylcholine α2 mRNA. This molecular effect is correlated to a decrease of imidacloprid sensitivity of cockroaches. Using RNA interference, we shown the key role of nicotinic acetylcholine α2 subunit in imidacloprid sensitivity. Thus, quantitative changes in insecticide targets lead to decreased sensitivity to insecticides. This parameter needs to be considered in order to develop sustainable insect resistance management strategies.
... α-Bgt-sensitive and -insensitive nAChR subtypes were also found in the DUM neurons. Two α-Bgt-insensitive receptors were identified as nAChR1, which are sensitive to IMI and selectively blocked by d-tubocurarine (d-TC), while nAChR2 is inhibited by mecamylamine [13,[15][16][17]. Together, these studies have been used to monitor and analyze the mode of action of neonicotinoid insecticides on insect nAChRs, in order to understand the mechanisms of resistance. ...
The functional expression of the cockroach Pameα7 nicotinic acetylcholine receptor subunit has been previously studied, and was found to be able to form a homomeric receptor when expressed in Xenopus laevis oocytes. In this study, we found that the neonicotinoid insecticide imidacloprid is unable to activate the cockroach Pameα7 receptor, although thiacloprid induces low inward currents, suggesting that it is a partial agonist. In addition, the co-application or 5 min pretreatment with 10 µM imidacloprid increased nicotine current amplitudes, while the co-application or 5 min pretreatment with 10 µM thiacloprid decreased nicotine-evoked current amplitudes by 54% and 28%, respectively. This suggesting that these two representatives of neonicotinoid insecticides bind differently to the cockroach Pameα7 receptor. Interestingly, the docking models demonstrate that the orientation and interactions of the two insecticides in the cockroach Pameα7 nAChR binding pocket are very similar. Electrophysiological results have provided evidence to suggest that imidacloprid and thiacloprid could act as modulators of the cockroach Pameα7 receptors.
... Sulfoxaflor induced high amplitude currents in DUM neurons, with the amplitude being at least equivalent to that produced by acetylcholine itself (Houchat et al., 2019). Moreover, the pharmacology of the block of sulfoxaflor-induced currents revealed that sulfoxaflor acts at both nAChR1 and nAChR2 subtypes, which adds to the DUM neuron nAChR complexity, where neonicotinoids are believed to be more subtype-selective (e.g., Bodereau-Dubois et al., 2012). The two discrete nAChR subtypes may potentially represent specific combinations of the different nAChR subunits (see below), but at present this level of detail remains unknown. ...
The sulfoximines, as exemplified by sulfoxaflor (Isoclast™active), are a relatively new class of nicotinic acetylcholine receptor (nAChR) competitive modulator (Insecticide Resistance Action Committee [IRAC] Group 4C) insecticides that provide control of a wide range of sap-feeding insect pests. The sulfoximine chemistry and sulfoxaflor exhibits distinct interactions with metabolic enzymes and nAChRs compared to other IRAC Group 4 insecticides such as the neonicotinoids (Group 4A). These distinctions translate to notable differences in the frequency and degree of cross-resistance between sulfoxaflor and other insecticides. Most insect strains exhibiting resistance to a variety of insecticides, including neonicotinoids, exhibited little to no cross-resistance to sulfoxaflor. To date, only two laboratory-based studies involving four strains (Koo et al. 2014, Chen et al. 2017) have observed substantial cross-resistance (>100 fold) to sulfoxaflor in neonicotinoid resistant insects. Where higher levels of cross-resistance to sulfoxaflor are observed the magnitude of that resistance is far less than that of the selecting neonicotinoid. Importantly, there is no correlation between presence of resistance to neonicotinoids (i.e., imidacloprid, acetamiprid) and cross-resistance to sulfoxaflor. This phenomenon is consistent with and can be attributed to the unique and differentiated chemical class represented by sulfoxalfor. Recent studies have demonstrated that high levels of resistance (resistance ratio = 124–366) to sulfoxaflor can be selected for in the laboratory which thus far appear to be associated with enhanced metabolism by specific cytochrome P450s, although other resistance mechanisms have not yet been excluded. One hypothesis is that sulfoxaflor selects for and is susceptible to a subset of P450s with different substrate specificity. A range of chemoinformatic, molecular modeling, metabolism and target-site studies have been published. These studies point to distinctions in the chemistry of sulfoxaflor, and its metabolism by enzymes associated with resistance to other insecticides, as well as its interaction with insect nicotinic acetylcholine receptors, further supporting the subgrouping of sulfoxaflor (Group 4C) separate from that of other Group 4 insecticides. Herein is an expansion of an earlier review (Sparks et al. 2013), providing an update that considers prior and current studies focused on the mode of action of sulfoxaflor, along with an analysis of the presently available resistance / cross-resistance studies, and implications and recommendations regarding resistance management.
