Pharmacological Actions of Carbamate Insecticides at Mammalian Melatonin Receptors

Glatfelter, Grant C.; Jones, Anthony; Rajnarayanan, Rajendram V.; Dubocovich, Margarita L.

doi:10.1124/jpet.120.000065

Cited by 12 publications

(15 citation statements)

References 91 publications

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Section: Resultsmentioning

confidence: 99%

“…While plastic chemicals have not previously been described to target MTNR1A or MTNR1B, several carbamate insecticides with high structural similarities to melatonin agonize or antagonize both receptors. 10,11 We did not confirm the following hits as they did not produce a dose-response relationship in the secondary screen: PVC Mix at prostaglandin E receptor 1 (PTGER1), Assorted Mix at prostaglandin E receptor 3 (PTGER3), PET Mix at AVPR2, PET Mix at lysophosphatidic acid receptor 5 (LPAR5), and TPP at Apelin receptor (APJ, Figure S7 A-F). The decreasing relationship for certain interactions (Assorted Mix at PTGER3) suggests nonspecific effects are partially or fully masking activation of the receptor, as discussed above in the case of MC3R.…”

Section: Adora1 Mc3r Mtnr1a and Mtnr1b Are Confirmed Targets Of Plast...mentioning

confidence: 98%

“…For instance, p,p’-DDT allosterically activates the human follitropin receptor (FSHR), 8 multiple phthalate esters inhibit the cannabinoid-1 (CB 1 ) receptor, 9 and certain carbamate insecticides activate or inhibit melatonin receptors. 10,11 While not comprehensive, these reports demonstrate that GPCRs are susceptible to known EDCs and other synthetic chemicals.…”

Section: Introductionmentioning

confidence: 99%

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Beyond the nucleus: Plastic chemicals activate G protein-coupled receptors

McPartland,

Stevens,

Bartosova

et al. 2023

Preprint

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FigureG protein-coupled receptors (GPCRs) are central mediators of cell signaling and physiological function. Despite their biological significance, GPCRs have not been widely studied in the field of toxicology. Herein, we investigated these receptors are novel targets of plastic chemicals using a high-throughput drug screening assay with 126 human non-olfactory GPCRs. In a first-pass screen, we tested the activity of triphenol phosphate, bisphenol A, and diethyl phthalate as well as three real-world mixtures of chemicals extracted from plastic food packaging covering all major polymer types. We found 11 GPCR-chemical interactions, of which the chemical mixtures exhibited the most robust activity at Adenosine receptor 1 (ADORA1) and Melatonin receptor 1 (MTNR1A) in a confirmatory secondary screen. We further confirmed that polyvinyl chloride and polyurethane products contain ADORA1 or MTNRA1 agonists using pharmacological knockdown experiments. Finally, an analysis of the associated gene ontology terms suggests that ADORA1 and MTNR1A activation may be linked to downstream effects on circadian and metabolic processes. Our findings exemplify the diversity of endpoints plastic chemicals can target and demonstrate the relevance of non-genomic pathways which have thus far remained unexplored.

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Section: Resultsmentioning

confidence: 99%

Section: Adora1 Mc3r Mtnr1a and Mtnr1b Are Confirmed Targets Of Plast...mentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Beyond the nucleus: Plastic chemicals activate G protein-coupled receptors

McPartland,

Stevens,

Bartosova

et al. 2023

Preprint

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“…OPs may also affect sleep via secondary mechanisms, such as inhibiting fatty acid amide hydrolase [356], the enzyme responsible for breaking down anandamide and oleamide [357], sleep-promoting lipids [358,359]. In addition to inhibiting AChE, carbamates may affect sleep by binding to melatonin receptors, phase-shifting circadian rhythms, and altering pineal melatonin synthesis [360][361][362][363]; an in silico binding study demonstrated the ability of carbaryl and carbofuran to bind the MT1 and MT2 receptors [361]. While not evaluated in the reviewed articles, neonicotinoids, a class of pesticides that act similarly to nicotine by binding to nicotinic acetylcholine receptors, have also been shown to disrupt sleep in honeybees [364,365].…”

Section: Pesticidesmentioning

confidence: 99%

Is exposure to chemical pollutants associated with sleep outcomes? A systematic review

Wallace

Gallagher

Peterson

et al. 2022

Preprint

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Background: Sleep disruption is a public health concern and environmental exposures that influence the biological processes underpinning sleep may contribute to impaired sleep health. However, the contributions of environmental chemical pollutants to sleep health have not been systematically investigated. Objectives: This systematic literature review sought to identify, evaluate, summarize, and synthesize the existing evidence between environmental chemical pollutant exposure and dimensions of sleep health in humans. We sought to evaluate potential mechanisms underlying exposure-outcome relationships and recommend areas for future research. Methods: Databases were searched for peer-reviewed published research on chemical environmental pollutants and sleep health and disorders with no date restriction up to the last search date of April 2021 (registered protocol PROSPERO # CRD42021256918), resulting in 9,918 records. Two reviewers independently screened identified records against inclusion and exclusion criteria, extracted study information, and performed risk of bias assessments. Results: We identified 204 studies of exposure to air pollution, exposures related to the Gulf War and other conflicts, endocrine disruptors, metals, pesticides, and solvents with dimensions of sleep health (architecture, duration, quality, timing) and sleep disorders (sleeping pill use, insomnia, sleep-disordered breathing) for inclusion in this review. Metals were the most frequently evaluated pollutants, while sleep maintenance/insomnia and quality were the most reported sleep outcomes. Synthesis of the evidence suggests mechanisms related to cholinergic signaling, neurotransmission, and inflammation as the most shared pathways. Discussion: Evidence indicates that exposure to particulate matter, secondhand smoke, dioxins and dioxin-like compounds, lead, mercury, pesticides, solvents, and exposures related to the Gulf War are associated with worse sleep health and disorders. Chemical pollutants are likely key environmental determinants of sleep health and disorders; thus, there is a need to improve measurement of pollutants and sleep, study rigor, and determine the populations most vulnerable to the effects of exposure.

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“…PVT neurons in rodents, monkeys, and humans highly express calretinin (CR), and the vast majority of CR+ neurons coexpress the glutamatergic neuronal marker Vglut2, but only 61.52 ± 2.62% of Vglut2+ neurons express CR, suggesting subpopulation heterogeneity within PVT neurons, and that CR could serve as a unique marker for PVT neurons 12–14 . PVT neurons also express 28 kDa calcium‐binding protein and a variety of neurotransmitter receptors, such as appetaminergic receptors, melatonergic receptors, and dopamine receptors, among which PVT neurons are characterized by dopamine D2 receptors (D2Rs) 15–18 . D2Rs are predominant on PVT neurons, and D2R+ and D2R− neurons are distributed in a gradient along the anterior–posterior axis of PVT, and these two types of neurons have different neurobiological functions in sleep–wake and emotional cognitive behaviors 18 …”

Section: Anatomy and Neurons Of Pvtmentioning

confidence: 99%

Research progress of the paraventricular thalamus in the regulation of sleep–wake and emotional behaviors

Liu

2022

Ibrain

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The paraventricular thalamus (PVT) is a major component of the midline structure of the thalamus. It is one of the nonspecific nuclei of the thalamus, which plays a great role in the regulation of cortical arousal. PVT, an important node in the central nervous system, sends widespread outputs to many brain regions and also accepts plentiful inputs from many brain regions to modulate diverse functions, including sleep–wake state, attention, memory, and pain. Recently, with the increasing prevalence of sleep disorders and mood disorders, people pay great attention to PVT, which was implicated in arousal and emotional behaviors. Therefore, the main purpose of this review is to illustrate the characteristic of PVT to provide a reference for future research.

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Pharmacological Actions of Carbamate Insecticides at Mammalian Melatonin Receptors

Cited by 12 publications

References 91 publications

Beyond the nucleus: Plastic chemicals activate G protein-coupled receptors

Beyond the nucleus: Plastic chemicals activate G protein-coupled receptors

Is exposure to chemical pollutants associated with sleep outcomes? A systematic review

Research progress of the paraventricular thalamus in the regulation of sleep–wake and emotional behaviors

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