Evidence map›Paper›PMID 29425245›Full record

ArticlePLoS neglected tropical diseases2018

Unique pharmacological properties of serotoninergic G-protein coupled receptors from cestodes.

Federico Camicia, Ana M Celentano, Malcolm E Johns, John D Chan, Lucas Maldonado, Hugo Vaca, Nicolás Di Siervi, Laura Kamentezky, Ana M Gamo, Silvia Ortega-Gutierrez and 4 more

Open access · goldAbstract read
In one paragraph

Article in PLoS neglected tropical diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
6.0field-weighted citation impact, top 4% 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

15 citing papers in PubMed, 33 citations in OpenAlex.

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  13. Histone deacetylase enzymes as potential drug targets of Neglected Tropical Diseases caused by cestodes.International journal for parasitology. Drugs and drug resistance · 2019
    Article
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  15. Article
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

14 authors at 5 institutions in 4 countries.

Federico CamiciaUniversidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPAM-UBA-CONICET), Facultad de Medicina, Buenos Aires, Argentina.
Ana M CelentanoUniversidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPAM-UBA-CONICET), Facultad de Medicina, Buenos Aires, Argentina.ORCID 0000-0001-7564-0908
Malcolm E JohnsDepartment of Pharmacology, University of Minnesota, Minneapolis, Minnesota, United States of America.
John D ChanDepartment of Biomedical Sciences, Iowa State University, Ames, Iowa, United States of America.
Lucas MaldonadoUniversidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPAM-UBA-CONICET), Facultad de Medicina, Buenos Aires, Argentina.ORCID 0000-0001-6965-1336
Hugo VacaUniversidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPAM-UBA-CONICET), Facultad de Medicina, Buenos Aires, Argentina.ORCID 0000-0002-5395-8402
Nicolás Di SierviUniversidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Investigaciones Farmacológicas (ININFA-UBA-CONICET), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina.ORCID 0000-0002-9035-8174
Laura KamentezkyUniversidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPAM-UBA-CONICET), Facultad de Medicina, Buenos Aires, Argentina.
Ana M GamoDepartamento de Química Orgánica I, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, Madrid, Spain.ORCID 0000-0002-7171-9878
Silvia Ortega-GutierrezDepartamento de Química Orgánica I, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, Madrid, Spain.
Mar Martin-FontechaDepartamento de Química Orgánica I, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, Madrid, Spain.ORCID 0000-0002-4848-0109
Carlos DavioUniversidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Investigaciones Farmacológicas (ININFA-UBA-CONICET), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina.
Jonathan S MarchantDepartment of Cell Biology, Neurobiology & Anatomy; Medical College of Wisconsin; Watertown Plank Road; Milwaukee; WI; United States of America.ORCID 0000-0001-6592-0877
Mara C RosenzvitUniversidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPAM-UBA-CONICET), Facultad de Medicina, Buenos Aires, Argentina.ORCID 0000-0002-5271-6321
Consejo Nacional de Investigaciones Científicas y Técnicas · ARUniversidad Complutense de Madrid · ESIowa State University · USMedical College of Wisconsin · USUniversity of Minnesota · US

Funding

Functional architecture of IP3-evoked local Ca2+ signalsR01GM088790 · NIGMS · UNIVERSITY OF MINNESOTA · PI MARCHANT, JONATHAN S, SLAMA, JAMES T · 2009 to 2025
$4.7M
(Re)generating new drug leads for schistosomiasisR21AI125821 · NIAID · UNIVERSITY OF MINNESOTA · PI MARCHANT, JONATHAN S · 2016 to 2018
$425k
A pharmacological screen for 'inactivating antagonists' at an essential parasite G protein coupled receptorR21AI130642 · NIAID · UNIVERSITY OF MINNESOTA · PI MARCHANT, JONATHAN S · 2017 to 2018
$422k
NIAID NIH HHS R21 AI125821NIAID NIH HHS R21 AI130642NIGMS NIH HHS R01 GM088790
6 · The paper itself

Abstract

backgroundCestodes are a diverse group of parasites, some of them being agents of neglected diseases. In cestodes, little is known about the functional properties of G protein coupled receptors (GPCRs) which have proved to be highly druggable targets in other organisms. Notably, serotoninergic G-protein coupled receptors (5-HT GPCRs) play major roles in key functions like movement, development and reproduction in parasites. METHODOLOGY/PRINCIPAL

findingsThree 5-HT GPCRs from Echinococcus granulosus and Mesocestoides corti were cloned, sequenced, bioinformatically analyzed and functionally characterized. Multiple sequence alignment with other GPCRs showed the presence of seven transmembrane segments and conserved motifs but interesting differences were also observed. Phylogenetic analysis grouped these new sequences within the 5-HT7 clade of GPCRs. Molecular modeling showed a striking resemblance in the spatial localization of key residues with their mammalian counterparts. Expression analysis using available RNAseq data showed that both E. granulosus sequences are expressed in larval and adult stages. Localization studies performed in E. granulosus larvae with a fluorescent probe produced a punctiform pattern concentrated in suckers. E. granulosus and M. corti larvae showed an increase in motility in response to serotonin. Heterologous expression revealed elevated levels of cAMP production in response to 5-HT and two of the GPCRs showed extremely high sensitivity to 5-HT (picomolar range). While each of these GPCRs was activated by 5-HT, they exhibit distinct pharmacological properties (5-HT sensitivity, differential responsiveness to ligands). CONCLUSIONS/SIGNIFICANCE: These data provide the first functional report of GPCRs in parasitic cestodes. The serotoninergic GPCRs characterized here may represent novel druggable targets for antiparasitic intervention.

Indexed as

Amino Acid MotifsAnimalsCestodaCestode InfectionsCloning, MolecularComputational BiologyEchinococcus granulosusLarvaMesocestoidesModels, MolecularPhylogenyProtein ConformationReceptors, G-Protein-CoupledSequence AlignmentSerotoninReceptors, G-Protein-CoupledSerotonin

Identifiers

PMID29425245
PMCPMC5823469
OpenAlexW2785677635

What OpenQuestion holds

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Registered trials

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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.