Evidence map›Paper›PMID 31759144›Full record

ArticleCellular and molecular gastroenterology and hepatology2020

Mu and Delta Opioid Receptors Are Coexpressed and Functionally Interact in the Enteric Nervous System of the Mouse Colon.

Jesse J DiCello, Simona E Carbone, Ayame Saito, Pradeep Rajasekhar, Rhian A Ceredig, Vi Pham, Celine Valant, Arthur Christopoulos, Nicholas A Veldhuis, Meritxell Canals and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cellular and molecular gastroenterology and hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

19 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Review
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  8. The role of morphine- and fentanyl-induced impairment of intestinal epithelial antibacterial activity in dysbiosis and its impact on the microbiota-gut-brain axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  9. The P2YBMC gastroenterology · 2024
    Article
  10. Review
  11. Article
  12. Opioid Use, Gut Dysbiosis, Inflammation, and the Nervous System.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2022
    Review
  13. Chronic Morphine Induces IL-18 in Ileum Myenteric Plexus Neurons Through Mu-opioid Receptor Activation in Cholinergic and VIPergic Neurons.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2022
    Article
  14. Opioid-Induced Pronociceptive Signaling in the Gastrointestinal Tract Is Mediated by Delta-Opioid Receptor Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022
    Article
  15. Article
  16. The Guts of the Opioid Crisis.Physiology (Bethesda, Md.) · 2021
    Article
  17. Optical clearing reveals TNBS-induced morphological changes of VGLUT2-positive nerve fibers in mouse colorectum.American journal of physiology. Gastrointestinal and liver physiology · 2021
    Article
  18. Article
  19. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 3 countries.

Jesse J DiCelloDrug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia; Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, Melbourne, VIC, Australia.
Simona E CarboneDrug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia; Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, Melbourne, VIC, Australia.
Ayame SaitoDrug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia; Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, Melbourne, VIC, Australia.
Pradeep RajasekharDrug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia; Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, Melbourne, VIC, Australia.
Rhian A CeredigCentre de la Recherche Nationale Scientifique, Université de Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France.
Vi PhamDrug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
Celine ValantDrug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
Arthur ChristopoulosDrug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia.
Nicholas A VeldhuisDrug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia; Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, Melbourne, VIC, Australia.
Meritxell CanalsDivision of Physiology, Pharmacology and Neuroscience, Queen's Medical Centre, School of Life Sciences, University of Nottingham, Nottingham, United Kingdom; Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, The Midlands, United Kingdom.
Dominique MassotteCentre de la Recherche Nationale Scientifique, Université de Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France.
Daniel P PooleDrug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia; Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville Campus, Melbourne, VIC, Australia; Department of Anatomy and Neuroscience, University of Melbourne, Parkville, VIC, Australia. Electronic address: Daniel.Poole@monash.edu.
Australian Research Council · AUMonash University · AUInstitut des Neurosciences Cellulaires et Intégratives · FRUniversity of Nottingham · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsFunctional interactions between the mu opioid receptor (MOR) and delta opioid receptor (DOR) represent a potential target for novel analgesics and may drive the effects of the clinically approved drug eluxadoline for the treatment of diarrhea-predominant irritable bowel syndrome. Although the enteric nervous system (ENS) is a likely site of action, the coexpression and potential interaction between MOR and DOR in the ENS are largely undefined. In the present study, we have characterized the distribution of MOR in the mouse ENS and examined MOR-DOR interactions by using pharmacologic and cell biology techniques.

methodsMOR and DOR expression was defined by using MORmCherry and MORmCherry-DOR-eGFP knockin mice. MOR-DOR interactions were assessed by using DOR-eGFP internalization assays and by pharmacologic analysis of neurogenic contractions of the colon.

resultsAlthough MOR was expressed by approximately half of all myenteric neurons, MOR-positive submucosal neurons were rarely observed. There was extensive overlap between MOR and DOR in both excitatory and inhibitory pathways involved in the coordination of intestinal motility. MOR and DOR can functionally interact, as shown through heterologous desensitization of MOR-dependent responses by DOR agonists. Functional evidence suggests that MOR and DOR may not exist as heteromers in the ENS. Pharmacologic studies show no evidence of cooperativity between MOR and DOR. DOR internalizes independently of MOR in myenteric neurons, and MOR-evoked contractions are unaffected by the sequestration of DOR.

conclusionsCollectively, these findings demonstrate that although MOR and DOR are coexpressed in the ENS and functionally interact, they are unlikely to exist as heteromers under physiological conditions.

Indexed as

Analgesics, OpioidAnimalsBenzamidesCHO CellsColonCricetulusEnteric Nervous SystemGastrointestinal MotilityGene Knock-In TechniquesGenes, ReporterGreen Fluorescent ProteinsHumansLuminescent ProteinsMiceMorphinePiperazines4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamideAnalgesics, OpioidBenzamidesCYM51010enhanced green fluorescent proteinGreen Fluorescent ProteinsLuminescent ProteinsMorphinePiperazinesPiperidinesReceptors, Opioid, deltaReceptors, Opioid, muRecombinant ProteinsRed Fluorescent ProteinG Protein-Coupled ReceptorHeterologous DesensitizationHeteromerOpioid Receptor

Identifiers

PMID31759144
PMCPMC7036548
OpenAlexW2990052641

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.