Evidence map›Paper›PMID 33916832›Full record

ArticleToxins2021

Pharmaceutical Assessment Suggests Locomotion Hyperactivity in Zebrafish Triggered by Arecoline Might Be Associated with Multiple Muscarinic Acetylcholine Receptors Activation.

Petrus Siregar, Gilbert Audira, Ling-Yi Feng, Jia-Hau Lee, Fiorency Santoso, Wen-Hao Yu, Yu-Heng Lai, Jih-Heng Li, Ying-Ting Lin, Jung-Ren Chen and 1 more

Open access · goldAbstract read
In one paragraph

Article in Toxins, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.0field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 23 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 1 country.

Petrus SiregarDepartment of Chemistry, Chung Yuan Christian University, Chung-Li, Taoyuan City 320314, Taiwan.
Gilbert AudiraDepartment of Chemistry, Chung Yuan Christian University, Chung-Li, Taoyuan City 320314, Taiwan.
Ling-Yi FengSchool of Pharmacy and Ph.D. Program in Toxicology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Jia-Hau LeeDepartment of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Fiorency SantosoDepartment of Bioscience Technology, Chung Yuan Christian University, Chung-Li, Taoyuan City 3020314, Taiwan.
Wen-Hao YuDepartment of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Yu-Heng LaiDepartment of Chemistry, Chinese Culture University, Taipei 11114, Taiwan.
Jih-Heng LiSchool of Pharmacy and Ph.D. Program in Toxicology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.ORCID 0000-0003-4712-9517
Ying-Ting LinDepartment of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.ORCID 0000-0001-8096-3402
Jung-Ren ChenDepartment of Biological Science & Technology, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan.
Chung-Der HsiaoDepartment of Chemistry, Chung Yuan Christian University, Chung-Li, Taoyuan City 320314, Taiwan.ORCID 0000-0002-6398-8672
Kaohsiung Medical University · TWChung Yuan Christian University · TWChinese Culture University · TWI-Shou University · TW

Funding

Ministry of Science and Technology, Taiwan MOST 107-2622-B-033-001-CC2 and MOST 108-2622-B-033-001-CC2 to C.-D.H.
6 · The paper itself

Abstract

Arecoline is one of the nicotinic acid-based alkaloids, which is found in the betel nut. In addition to its function as a muscarinic agonist, arecoline exhibits several adverse effects, such as inducing growth retardation and causing developmental defects in animal embryos, including zebrafish, chicken, and mice. In this study, we aimed to study the potential adverse effects of waterborne arecoline exposure on zebrafish larvae locomotor activity and investigate the possible mechanism of the arecoline effects in zebrafish behavior. The zebrafish behavior analysis, together with molecular docking and the antagonist co-exposure experiment using muscarinic acetylcholine receptor antagonists were conducted. Zebrafish larvae aged 96 h post-fertilization (hpf) were exposed to different concentrations (0.001, 0.01, 0.1, and 1 ppm) of arecoline for 30 min and 24 h, respectively, to find out the effect of arecoline in different time exposures. Locomotor activities were measured and quantified at 120 hpf. The results showed that arecoline caused zebrafish larvae locomotor hyperactivities, even at a very low concentration. For the mechanistic study, we conducted a structure-based molecular docking simulation and antagonist co-exposure experiment to explore the potential interactions between arecoline and eight subtypes, namely, M1a, M2a, M2b, M3a, M3b, M4a, M5a, and M5b, of zebrafish endogenous muscarinic acetylcholine receptors (mAChRs). Arecoline was predicted to show a strong binding affinity to most of the subtypes. We also discovered that the locomotion hyperactivity phenotypes triggered by arecoline could be rescued by co-incubating it with M1 to M4 mAChR antagonists. Taken together, by a pharmacological approach, we demonstrated that arecoline functions as a highly potent hyperactivity-stimulating compound in zebrafish that is mediated by multiple muscarinic acetylcholine receptors.

Indexed as

AnimalsArecolineBehavior, AnimalDose-Response Relationship, DrugLocomotionMolecular Docking SimulationMuscarinic AgonistsMuscarinic AntagonistsPhotoperiodProtein BindingReceptors, MuscarinicSignal TransductionTime FactorsZebrafishArecolineMuscarinic AgonistsMuscarinic AntagonistsReceptors, Muscarinicantagonistarecolinebetel nutlocomotionmolecular dockingmuscarinic acetylcholine receptorzebrafish

Identifiers

PMID33916832
PMCPMC8066688
OpenAlexW3143344169

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.