A point mutation in the β‐adrenergic‐like octopamine receptor: possible association with amitraz resistance

Takata, Mizuki; Misato, Seishi; Ozoe, Fumiyo; Ozoe, Yoshihisa

doi:10.1002/ps.5921

Cited by 18 publications

(22 citation statements)

References 36 publications

(54 reference statements)

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“…Moreover, DPMF was confirmed to be a more potent octopamine receptor agonist than amitraz itself, indicating that amitraz undergoes metabolic activation. Site-directed mutagenesis studies clearly showed that amitraz and DPMF act as orthosteric antagonists [73]. These groundbreaking studies provided evidence that targetsite insensitivity significantly contributes to the widespread amitraz resistance [73].…”

Section: Octopamine Receptors As Molecular Targets Of Insecticidesmentioning

confidence: 98%

PaOctβ2R: Identification and Functional Characterization of an Octopamine Receptor Activating Adenylyl Cyclase Activity in the American Cockroach Periplaneta americana

Blenau

Bremer

Schwietz

et al. 2022

IJMS

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Biogenic amines constitute an important group of neuroactive substances that control and modulate various neural circuits. These small organic compounds engage members of the guanine nucleotide-binding protein coupled receptor (GPCR) superfamily to evoke specific cellular responses. In addition to dopamine- and 5-hydroxytryptamine (serotonin) receptors, arthropods express receptors that are activated exclusively by tyramine and octopamine. These phenolamines functionally substitute the noradrenergic system of vertebrates Octopamine receptors that are the focus of this study are classified as either α- or β-adrenergic-like. Knowledge on these receptors is scarce for the American cockroach (Periplaneta americana). So far, only an α–adrenergic-like octopamine receptor that primarily causes Ca2+ release from intracellular stores has been studied from the cockroach (PaOctα1R). Here we succeeded in cloning a gene from cockroach brain tissue that encodes a β-adrenergic-like receptor and leads to cAMP production upon activation. Notably, the receptor is 100-fold more selective for octopamine than for tyramine. A series of synthetic antagonists selectively block receptor activity with epinastine being the most potent. Bioinformatics allowed us to identify a total of 19 receptor sequences that build the framework of the biogenic amine receptor clade in the American cockroach. Phylogenetic analyses using these sequences and receptor sequences from model organisms showed that the newly cloned gene is an β2-adrenergic-like octopamine receptor. The functional characterization of PaOctβ2R and the bioinformatics data uncovered that the monoaminergic receptor family in the hemimetabolic P. americana is similarly complex as in holometabolic model insects like Drosophila melanogaster and the honeybee, Apis mellifera. Thus, investigating these receptors in detail may contribute to a better understanding of monoaminergic signaling in insect behavior and physiology.

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Section: Octopamine Receptors As Molecular Targets Of Insecticidesmentioning

confidence: 98%

PaOctβ2R: Identification and Functional Characterization of an Octopamine Receptor Activating Adenylyl Cyclase Activity in the American Cockroach Periplaneta americana

Blenau

Bremer

Schwietz

et al. 2022

IJMS

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“…For instance, OARs have drawn widespread attention as targets for formamidine-type insecticides/ acaricides [chlordimeform, amitraz and N-2,4-dimethylphenyl-N 0methylformamidine (DPMF), a metabolite of amitraz], and are crucial in the development of current insecticides. [13][14][15] OARs can be further grouped as either ⊍-OARs (⊍-adrenergic-like octopamine receptors) or ⊎-OARs (⊎-adrenergic-like octopamine receptors) according to their sequence homology. 16 ⊎-OARs are further put into three categories according to differences in their genetic and functional characterization.…”

Section: Introductionmentioning

confidence: 99%

Phenyl imidazolidin‐2‐ones antagonize a β‐adrenergic‐like octopamine receptor in diamondback moth (Plutella xylostella)

Deng

Guo

et al. 2021

Pest Management Science

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BACKGROUND: The diamondback moth (Plutella xylostella) is one of the most destructive lepidopteran pests on cruciferous vegetables. However, resistance has emerged to current chemical and biological insecticides used for P. xylostella control, indicating the necessity of screening new targets on P. xylostella, and finding new insecticides against P. xylostella. In particular, octopamine receptors are representative G protein-coupled receptors found only in invertebrates and are potential targets for identifying novel insecticides.RESULTS: A ⊎-adrenergic-like octopamine receptor gene (PxOA2B1) was cloned, and its pharmacological characteristics in P. xylostella were studied. The results demonstrated that octopamine could activate the PxOA2B1 receptor, with a half-maximal effective concentration (EC 50 ) of 49.5 nM. Amitraz, an insecticide and acaricide, and its metabolite (N-2,4-dimethylphenyl-N 0methylformamidine; DPMF) were also found to act as PxOAB1R agonists. We synthesized phenyl imidazolidin-2-one derivatives 3a-h using DPMF as the lead compound, and compounds 3a-h showed similar antagonist activities as phentolamine, mianserin and chlorpromazine. In particular, 3d, with an EC 50 of 25.2 nM, showed very similar antagonist activity to mianserin.CONCLUSION: This research found that PxOAB1R might be a potential target for P. xylostella control. Phenyl imidazolidin-2-ones could be novel potential antagonists targeted at octopamine receptors and would be useful tools for the design and development of novel insecticides.

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“…A correlation analysis of the mutation frequency and the phenotypic traits confirmed the I61F site mutation to be associated to amitraz resistance 15 . This conclusion was further verified in the silkworm cell line 17 . Besides the octopamine receptors, ATP‐binding cassette transporters (ABC transporters) have also been shown to be involved in the detoxification and transport of amitraz metabolites.…”

Section: Discussionmentioning

confidence: 72%

“…15 This conclusion was further verified in the silkworm cell line. 17 Besides the octopamine receptors, ATP-binding cassette transporters (ABC transporters) have also been shown to be involved in the detoxification and transport of amitraz metabolites. Through immunolocalization and RNAi analysis, it was previously found that ABCB10 of R. microplus can transport and detoxify amitraz in midgut cells 89 ; subsequent analysis of differential gene expression confirmed the high expression level of this transporter in acaricideresistant cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, given the large‐scale use of this pesticide, there is a high risk for P. citri to develop resistance. But there is currently no report of this on P. citri , as the focus of research to date has primarily been on ticks 14–17 . Therefore, further investigations of the mechanisms underlying the potential development of resistance to amitraz in P. citri may help guide the rational use of amitraz in the field.…”

Section: Introductionmentioning

confidence: 99%

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Whole genome sequencing and bulked segregant analysis suggest a new mechanism of amitraz resistance in the citrus red mite, Panonychus citri (Acari: Tetranychidae)

Cong

Pan

et al. 2021

Pest Management Science

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BACKGROUND Amitraz is a broad‐spectrum insecticide/acaricide for the control of aphids, psyllids, ticks and mites. Current evidence suggests that ticks and phytophagous mites have developed strong resistance to amitraz. Previous studies have shown that multiple mechanisms are associated with amitraz resistance in ticks, but very few reports have involved Panonychus citri. We therefore used whole genome sequencing and bulked segregant analysis (BSA) to identify the mechanism underlying P. citri's resistance to amitraz. RESULTS High‐quality assembly of the whole P. citri genome was completed, resulting in a genome of approximately 83.97 Mb and a contig N50 of approximately 1.81 Mb. Gene structure predictions revealed 11 577 genes, of which 10 940 genes were annotated. Trait‐associated regions in the genome were mapped with bulked segregant analysis and 38 candidate SNPs were obtained, of which T752C had the strongest correlation with the resistant trait, located at the 5′ untranslated region (UTR) of the β‐2R adrenergic‐like octopamine receptor gene. The mutation resulted in the formation of a short hairpin loop structure in mRNA and gene expression was down‐regulated by more than 50% in the amitraz‐resistant strain. Validation of the T752C mutation in field populations of P. citri found that the correlation between the resistance ratio and the base mutation was 94.40%. CONCLUSION Our results suggest that this 5′ UTR mutation of the β‐2R octopamine receptor gene, confers amitraz resistance in P. citri. This discovery provides a new explanation for the mechanism of pest resistance: base mutations in the 5′ untranslated region of target gene may regulate the susceptibility of pests to pesticides.

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A point mutation in the β‐adrenergic‐like octopamine receptor: possible association with amitraz resistance

Cited by 18 publications

References 36 publications

PaOctβ2R: Identification and Functional Characterization of an Octopamine Receptor Activating Adenylyl Cyclase Activity in the American Cockroach Periplaneta americana

PaOctβ2R: Identification and Functional Characterization of an Octopamine Receptor Activating Adenylyl Cyclase Activity in the American Cockroach Periplaneta americana

Phenyl imidazolidin‐2‐ones antagonize a β‐adrenergic‐like octopamine receptor in diamondback moth (Plutella xylostella)

Whole genome sequencing and bulked segregant analysis suggest a new mechanism of amitraz resistance in the citrus red mite, Panonychus citri (Acari: Tetranychidae)

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