The role of mechanical forces and adenosine in the regulation of intestinal enterochromaffin cell serotonin secretion
| العنوان: | The role of mechanical forces and adenosine in the regulation of intestinal enterochromaffin cell serotonin secretion |
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| المؤلفون: | Bauer E. Sumpio, Mark Kidd, Atle van Beelen Granlund, Bernhard Svejda, Arne K. Sandvik, Andrew T. Timberlake, Bjorn I. Gustafsson, Alexander L. Chin, Irvin M. Modlin, Roswitha Pfragner |
| المصدر: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 302:G397-G405 |
| بيانات النشر: | American Physiological Society, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Male, Adenosine, Physiology, Receptor expression, MAP Kinase Kinase 1, Gene Expression, Hormones and Signaling, Adenosine-5'-(N-ethylcarboxamide), Tryptophan Hydroxylase, Vesicular monoamine transporter 1, Mechanotransduction, Cellular, Serotonin secretion, chemistry.chemical_compound, Crohn Disease, Acetamides, Cyclic AMP, Phosphorylation, Cyclic AMP Response Element-Binding Protein, Receptor, Cells, Cultured, TPH1, Gastroenterology, Middle Aged, Adenosine A2 Receptor Antagonists, Enterochromaffin cell, Female, Signal Transduction, medicine.drug, Adult, Serotonin, medicine.medical_specialty, Adenosine A2 Receptor Agonists, Receptor, Adenosine A2A, Colon, MAP Kinase Signaling System, Biology, Receptor, Adenosine A2B, Cell Line, Tumor, Physiology (medical), Internal medicine, Enterochromaffin Cells, medicine, Humans, Aged, Hepatology, Receptor, Adenosine A1, Receptor, Adenosine A3, Cyclic AMP-Dependent Protein Kinases, Endocrinology, chemistry, Purines, Vesicular Monoamine Transport Proteins, Stress, Mechanical, Proto-Oncogene Proteins c-akt, Adenosine A2B receptor |
| الوصف: | 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. |
| تدمد: | 1522-1547 0193-1857 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::969771ebdfa527f44ee5854e97cffc73Test https://doi.org/10.1152/ajpgi.00087.2011Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....969771ebdfa527f44ee5854e97cffc73 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221547 01931857 |
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