Evidence map›Paper›PMID 25724083›Full record

ArticleNeuropharmacology2015

Neuropharmacology of purinergic receptors in human submucous plexus: Involvement of P2X₁, P2X₂, P2X₃ channels, P2Y and A₃ metabotropic receptors in neurotransmission.

A Liñán-Rico, J E Wunderlich, J T Enneking, D R Tso, I Grants, K C Williams, A Otey, K Michel, M Schemann, B Needleman and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuropharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.9field-weighted citation impact, top 7% 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

17 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
  2. Review
  3. Enteric nervous system as a therapeutic target in gastrointestinal disorders.World journal of gastrointestinal pharmacology and therapeutics · 2025
    Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Fluorescent CaScience signaling · 2018
    Article
  11. Purinergic drug targets for gastrointestinal disorders.Current opinion in pharmacology · 2017
    Review
  12. Article
  13. Article
  14. Purinergic Signalling: Therapeutic Developments.Frontiers in pharmacology · 2017
    Review
  15. Review
  16. Article
  17. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 2 countries.

A Liñán-RicoDepartment of Anesthesiology, The Wexner Medical Center at The Ohio State University, Columbus, OH, USA.
J E WunderlichDepartment of Anesthesiology, The Wexner Medical Center at The Ohio State University, Columbus, OH, USA.
J T EnnekingDepartment of Anesthesiology, The Wexner Medical Center at The Ohio State University, Columbus, OH, USA.
D R TsoDepartment of Anesthesiology, The Wexner Medical Center at The Ohio State University, Columbus, OH, USA.
I GrantsDepartment of Anesthesiology, The Wexner Medical Center at The Ohio State University, Columbus, OH, USA.
K C WilliamsDivision of Pediatric Gastroenterology, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
A OteyDepartment of Anesthesiology, The Wexner Medical Center at The Ohio State University, Columbus, OH, USA.
K MichelHuman Biology, Technische Universität München, Freising, Germany.
M SchemannHuman Biology, Technische Universität München, Freising, Germany.
B NeedlemanDepartment of Surgery, The Wexner Medical Center at The Ohio State University, Columbus, OH, USA.
A HarzmanDepartment of Surgery, The Wexner Medical Center at The Ohio State University, Columbus, OH, USA.
F L ChristofiDepartment of Anesthesiology, The Wexner Medical Center at The Ohio State University, Columbus, OH, USA. Electronic address: Fedias.Christofi@osumc.edu.
The Ohio State University Wexner Medical Center · USTechnical University of Munich · DENationwide Children's Hospital · US

Funding

PURINERGIC REGULATION OF ENTERIC NEURAL REFLEXESR01DK044179 · NIDDK · OHIO STATE UNIVERSITY · PI CHRISTOFI, FEDIAS LEONTIOU · 1999 to 2011
$2.7M
Neuroimaging of Purinergic Pathways in the Human ENSR01DK093499 · NIDDK · OHIO STATE UNIVERSITY · PI CHRISTOFI, FEDIAS LEONTIOU · 2012 to 2015
$1.3M
Ednrb Regulation of Gastrointestinal MotilityK08DK078035 · NIDDK · VANDERBILT UNIVERSITY · PI WILLIAMS, KENT CHARLES · 2009 to 2013
$725k
ADENOSINE RECEPTORS IN THE DIGESTIVE TRACTR29DK044179 · NIDDK · OHIO STATE UNIVERSITY · PI CHRISTOFI, FEDIAS L. · 1992 to 1996
–
INVERTED SPOT LASER SCANNING CONFOCAL MICROSCOPES10RR011434 · NCRR · OHIO STATE UNIVERSITY · PI CHRISTOFI, FEDIAS L. · 1996 to 1996
–
NCRR NIH HHS S10RR11434NIDDK NIH HHS 5K08DK078035NIDDK NIH HHS DK044179NIDDK NIH HHS DK093499NIDDK NIH HHS K08 DK078035NIDDK NIH HHS R01 DK044179NIDDK NIH HHS R01 DK093499
6 · The paper itself

Abstract

rationaleThe role of purinergic signaling in human ENS is not well understood. We sought to further characterize the neuropharmacology of purinergic receptors in human ENS and test the hypothesis that endogenous purines are critical regulators of neurotransmission. EXPERIMENTAL APPROACH: LSCM-Fluo-4/(Ca(2+))-imaging of postsynaptic Ca(2+) transients (PSCaTs) was used as a reporter of synaptic transmission evoked by fiber tract electrical stimulation in human SMP surgical preparations. Pharmacological analysis of purinergic signaling was done in 1,556 neurons (identified by HuC/D-immunoreactivity) in 235 ganglia from 107 patients; P2XR-immunoreactivity was evaluated in 19 patients. Real-time MSORT (Di-8-ANEPPS) imaging tested effects of adenosine on fast excitatory synaptic potentials (fEPSPs).

resultsSynaptic transmission is sensitive to pharmacological manipulations that alter accumulation of extracellular purines: Apyrase blocks PSCaTs in a majority of neurons. An ecto-NTPDase-inhibitor 6-N,N-diethyl-D-β,γ-dibromomethyleneATP or adenosine deaminase augments PSCaTs. Blockade of reuptake/deamination of eADO inhibits PSCaTs. Adenosine inhibits fEPSPs and PSCaTs (IC50 = 25 µM), sensitive to MRS1220-antagonism (A3AR). A P2Y agonist ADPβS inhibits PSCaTs (IC50 = 111 nM) in neurons without stimulatory ADPbS responses (EC50 = 960 nM). ATP or a P2X1,2,2/3 (α,β-MeATP) agonist evokes fast, slow, biphasic Ca(2+) transients or Ca(2+) oscillations (ATP,EC50 = 400 mM). PSCaTs are sensitive to P2X1 antagonist NF279. Low (20 nM) or high (5 µM) concentrations of P2X antagonist TNP-ATP block PSCaTs in different neurons; proportions of neurons with P2XR-immunoreactivity follow the order P2X2 > P2X1 >> P2X3; P2X1 + P2X2 and P2X3 + P2X2 are co-localized. RT-PCR identified mRNA-transcripts for P2X1-7, P2Y1,2,12-14R.

conclusionsPurines are critical regulators of neurotransmission in human ENS. Purinergic signaling involves P2X1, P2X2, P2X3 channels, P2X1 + P2X2 co-localization and inhibitory P2Y or A3 receptors. These are potential novel therapeutic targets for neurogastroenterology.

Indexed as

Adenosine TriphosphateCalciumColectomyElectric StimulationExcitatory Postsynaptic PotentialsHumansImmunohistochemistryNeuronsPurinergic AgentsReceptors, PurinergicSubmucous PlexusSynaptic TransmissionVoltage-Sensitive Dye ImagingAdenosine TriphosphateCalciumPurinergic AgentsReceptors, PurinergicA(3) inhibitory receptorsATPEndogenous adenosineHuman enteric nervous systemInhibitory P2Y receptorsP2X channelsPurinergic synaptic transmissionSubmucous plexus

Identifiers

PMID25724083
PMCPMC4466061
OpenAlexW2085683228

What OpenQuestion holds

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LicenceTDM
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.