ArticleInflammatory bowel diseases2013
Purinergic autocrine regulation of mechanosensitivity and serotonin release in a human EC model: ATP-gated P2X3 channels in EC are downregulated in ulcerative colitis.
Article in Inflammatory bowel diseases, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Purinergic signaling in the gut neuro-glial-immune axis: mechanisms of homeostasis, inflammation, and gastrointestinal dysfunction.Frontiers in gastroenterology (Lausanne, Switzerland) · 2026Review
- Modulation of the Mechanosensory Matrisome by Serotonergic Signaling.Results and problems in cell differentiation · 2026Review
- GDNF signaling modulation by Akkermansia muciniphila ameliorates constipation-depression comorbidity in Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Article
- Untargeted serum metabolomic analysis reveals a role for purinergic signaling in FPIES.The Journal of allergy and clinical immunology · 2023Article
- Examination of the mechanism of Piezo ion channel in 5-HT synthesis in the enterochromaffin cell and its association with gut motility.Frontiers in endocrinology · 2023Article
- Role of Ion Channels in the Chemotransduction and Mechanotransduction in Digestive Function and Feeding Behavior.International journal of molecular sciences · 2022Review
- A population of gut epithelial enterochromaffin cells is mechanosensitive and requires Piezo2 to convert force into serotonin release.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- In Pursuit of the Epithelial Mechanosensitivity Mechanisms.Frontiers in endocrinology · 2018Review
- Clopidogrel IBS Patients Have Higher Incidence of Gastrointestinal Symptoms Influenced by Age and Gender.Digestive diseases and sciences · 2017Article
- Mechanosensitive ion channel Piezo2 is inhibited by D-GsMTx4.Channels (Austin, Tex.) · 2017Article
- UTP - Gated Signaling Pathways of 5-HT Release from BON Cells as a Model of Human Enterochromaffin Cells.Frontiers in pharmacology · 2017Article
- Mechanosensitive ion channel Piezo2 is important for enterochromaffin cell response to mechanical forces.The Journal of physiology · 2017Article
- Mechanosensitive Piezo Channels in the Gastrointestinal Tract.Current topics in membranes · 2017Review
- Molecular Signaling and Dysfunction of the Human Reactive Enteric Glial Cell Phenotype: Implications for GI Infection, IBD, POI, Neurological, Motility, and GI Disorders.Inflammatory bowel diseases · 2016Article
- What goes around comes around: novel pharmacological targets in the gut-brain axis.Therapeutic advances in gastroenterology · 2016Review
- Mechanosensory Signaling in Enterochromaffin Cells and 5-HT Release: Potential Implications for Gut Inflammation.Frontiers in neuroscience · 2016Review
- Purinergic Signaling in Gut Inflammation: The Role of Connexins and Pannexins.Frontiers in neuroscience · 2016Review
- Neuropharmacology of purinergic receptors in human submucous plexus: Involvement of P2X₁, P2X₂, P2X₃ channels, P2Y and A₃ metabotropic receptors in neurotransmission.Neuropharmacology · 2015Article
- Expression of P2X3 and P2X 5 myenteric receptors varies during the intestinal postnatal development in the guinea pig.Cellular and molecular neurobiology · 2014Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundAlterations in 5-hydroxytryptamine (HT) signaling in inflamed gut may contribute to pathogenesis of inflammatory bowel diseases. Adenosine 5'-triphosphate (ATP) regulates mucosal-mechanosensory reflexes and ATP receptors are sensitive to mucosal inflammation. Yet, it remains unknown whether ATP can modulate 5-HT signaling in enterochromaffin cells (EC). We tested the novel purinergic hypothesis that ATP is a critical autocrine regulator of EC mechanosensitivity and whether EC expression of ATP-gated P2X3-ion channels is altered in inflammatory bowel diseases.
methodsLaser confocal (fluo-4) Ca imaging was performed in 1947 BON cells. Chemical stimulation or mechanical stimulation (MS) was used to study 5-HT or ATP release in human BON or surgical mucosal specimens, and purine receptors by reverse transcription-polymerase chain reaction, Western Blot, or P2X3-immunoreactivity in BON or 5-HT human EC (hEC) in 11 control and 10 severely inflamed ulcerative colitis (UC) cases.
resultsATP or MS triggered Ca-transients or 5-HT release in BON. ATP or adenosine diphosphate increased 5-HT release 5-fold. MS caused ATP release, detected after 5'ecto-ATPase inhibition by ARL67156. ARL67156 augmented and apyrase blocked Ca/5-HT mechanosensitive responses. 2-Methyl-thio-adenosine diphosphate 5'-monophosphate-evoked (P2Y1,12) or mechanically-evoked responses were blocked or augmented by a P2Y1,12 antagonist, MRS2179, in different cells or inhibited by U73122. A P2Y12 antagonist, 2MeSAMP, augmented responses. A P2X1,3 agonist, α,β-MeATP, triggered Ca responses, whereas a P2X1,2/3,3 antagonist, 2',3'-O-(2,4,6-trinitrophenyl)-ATP, blocked mechanical responses or cell-surface 5'ATP- labeling. In hEC, α,β-MeATP stimulated 5-HT release. In UC, P2X3-immunoreactivity decreased from 15% to 0.2% of 5-HThECs. Human mucosa and BON expressed P2X1, P2X3, P2X4, P2X5, P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, and P2Y12R-messenger RNA transcripts.
conclusionsATP is a critical determinant of mechanosensation and 5-HT release via autocrine activation of slow P2Y1-phospholipase C/inositol-1,4,5-triphosphate-Ca or inhibitory P2Y12-purinergic pathways, and fast ATP-gated P2X3-channels. UC downregulation of P2X3-channels (or A2B) is postulated to mediate abnormal 5-HT signaling.
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