ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2012
The role of mechanical forces and adenosine in the regulation of intestinal enterochromaffin cell serotonin secretion.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 66 citations in OpenAlex.
- Piezo knockdown reduces 5‑hydroxytryptamine release from enterochromaffin cells and exacerbates intestinal dyskinesia in mice with functional constipation.International journal of molecular medicine · 2025Article
- Therapeutic potential of adenosine receptor modulators in cancer treatment.RSC advances · 2025Review
- Measurement of Real-Time Serotonin Dynamics from Human-Derived Gut Organoids.Analytical chemistry · 2025Article
- Long-term tuina can inhibit the occurrence of gastroparesis by protecting gastrointestinal function in diabetic rats.Frontiers in endocrinology · 2025Article
- Current Understanding of the Role of Adenosine Receptors in Cancer.Molecules (Basel, Switzerland) · 2024Review
- Mechano-sensitivity of β2-adrenoceptors enhances constitutive activation of cAMP generation that is inhibited by inverse agonists.Communications biology · 2024Article
- Evaluation of the serotonin pathway as a biomarker in cholangiocarcinoma.Journal of gastrointestinal oncology · 2023Article
- Mechanosensing Piezo channels in gastrointestinal disorders.The Journal of clinical investigation · 2023Review
- Untargeted serum metabolomic analysis reveals a role for purinergic signaling in FPIES.The Journal of allergy and clinical immunology · 2023Article
- The gut dysbiosis-cancer axis: illuminating novel insights and implications for clinical practice.Frontiers in pharmacology · 2023Review
- Gut feelings: mechanosensing in the gastrointestinal tract.Nature reviews. Gastroenterology & hepatology · 2022Review
- Digital Spatial Profiling Reveals Functional Shift of Enterochromaffin Cell in Patients With Ulcerative Colitis.Frontiers in cell and developmental biology · 2022Article
- Potential Roles of Enterochromaffin Cells in Early Life Stress-Induced Irritable Bowel Syndrome.Frontiers in cellular neuroscience · 2022Review
- Subepithelial Serotonin Reduces Small Intestinal Epithelial Cell Tightness via Reduction of Occluding Expression.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2022Article
- Microbiomics in Collusion with the Nervous System in Carcinogenesis: Diagnosis, Pathogenesis and Treatment.Microorganisms · 2021Review
- Magnetically-propelled fecal surrogates for modeling the impact of solid-induced shear forces on primary colonic epithelial cells.Biomaterials · 2021Article
- Luteolin suppresses 5-hydroxytryptamine elevation in stimulated RBL-2H3 cells and experimental colitis mice.Journal of clinical biochemistry and nutrition · 2021Article
- The Role of the Gut Microbiota in the Gut-Brain Axis in Obesity: Mechanisms and Future Implications.International journal of molecular sciences · 2021Review
- Targeting Mechano-Transcription Process as Therapeutic Intervention in Gastrointestinal Disorders.Frontiers in pharmacology · 2021Review
- Pathophysiologic Role of Neurotransmitters in Digestive Diseases.Frontiers in physiology · 2021Review
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Enterochromaffin (EC) cells of the diffuse neuroendocrine cell system secrete serotonin (5-HT) with activation of gut motility, secretion, and pain. These cells express adenosine (ADORA) receptors and are considered to function as mechanosensors. Physiological pathways mediating mechanosensitivity and adenosine responsiveness remain to be fully elucidated, as do their roles in inflammatory bowel disease (IBD) and neoplasia. Pure (98-99%) FACS-sorted normal and IBD human EC cells and neoplastic EC cells (KRJ-I) were studied. IBD-EC cells and KRJ-I overexpressed ADORA2B. NECA, a general ADORA receptor agonist, stimulated, whereas the A2B receptor antagonist MRS1754 inhibited, 5-HT release (EC50 = 1.8 × 10-6 M; IC50 = 3.7 × 10-8 M), which was associated with corresponding alterations in intracellular cAMP levels and pCREB (Ser133). Mechanical stimulation using a rhythmic flex model induced transcription and activation of Tph1 (tryptophan hydroxylase) and VMAT₁ (vesicular monoamine transporter 1) and the release of 5-HT, which could be inhibited by MRS1754 and amplified by NECA. Secretion was also inhibited by H-89 (PKA inhibitor) while Tph1 and VMAT₁ transcription was regulated by PKA/MAPK and PI₃K-mediated signaling. Normal and IBD-EC cells also responded to NECA and mechanical stimulation with PKA activation, cAMP production, and 5-HT release, effects reversible by MRS1754. EC cells express stimulatory ADORA2B, and rhythmic stretch induces A2B activation, PKA/MAPK/IP3-dependent transcription, and PKA-dependent secretion of 5-HT synthesis and secretion. Receptor expression is amplified in IBD and neoplasia, and 5-HT release is increased. Determination of factors that regulate EC cell function are necessary for understanding its role as a mechanosensory cell and to facilitate the development of agents that can selectively target cell function in EC cell-associated disease.
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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.