Disorders of gastrointestinal function are common and significantly reduce quality-of-life, as well as negatively impacting healthcare costs. Consequently, there is much interest in understanding the pathogenesis of these disorders. Increasing, albeit as yet limited, evidence has implicated alterations in 5-hydroxytryptamine (5-HT) release, and the subsequent interaction of 5-HT with specific 5-HT receptor subtypes, in the altered gut function of patients with irritable bowel syndrome (IBS) and other functional bowel diseases. Alterations to enterochromaffin cells and/or 5-HT signaling can result in gastrointestinal dysmotility, visceral hypersensitivity and secretomotor abnormalities in the gut. Evidence is beginning to link disturbed 5-HT physiology with the pathophysiology of diarrhea and constipation in IBS, and with slow-transit constipation. This review discusses the current evidence on the pathobiology of these systems.
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J Allergy Clin Immunol
December 2024
Institute of Allergology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology, Berlin, Germany. Electronic address:
Histamine (CHN, molecular weight 111.15 g/mol) is a well-studied endogenous biogenic amine composed of an imidazole ring attached to an ethylamine side chain. It has a limited half-life of a few minutes within tissues and in circulation.
View Article and Find Full Text PDFToxicol Sci
December 2024
Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
Drug-induced emesis is one of the major symptoms of gastrointestinal toxicity. Preclinical risk assessment of emesis has been challenging owing to the lack of suitable animal models or in vitro assay systems. One of the triggers of emesis is an excessive serotonin (5-HT) release from enterochromaffin (EC) cells in the intestinal tract, which activates the vomiting center in the brain stem and elicits the vomiting reflex.
View Article and Find Full Text PDFTransplantation
January 2025
Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada.
Background: Induced pluripotent stem cells (iPSCs) offer the potential to generate autologous iPSC-derived islets (iPSC islets), however, remain limited by scalability and product safety.
Methods: Herein, we report stagewise characterization of cells generated following a bioreactor-based differentiation protocol. Cell characteristics were assessed using flow cytometry, quantitative reverse transcription polymerase chain reaction, patch clamping, functional assessment, and in vivo functional and immunohistochemistry evaluation.
Int J Tryptophan Res
December 2024
Department of Public Health, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Background: Biomarkers for psychological stress have been examined and the "gut-microbiota-brain axis" is currently attracting attention. An intervention study reported improvements in both the intestinal environment and psychological stress. However, the relationship between psychological stress scores and urinary 5-hydroxytryptamine (u-5-HT), produced by enterochromaffin cells in the intestinal tract, has not yet been investigated over time in healthy subjects under psychological stress.
View Article and Find Full Text PDFJ Physiol
December 2024
Institute of Metabolic Science and MRC Metabolic Diseases Unit, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Gut hormones control intestinal function, metabolism and appetite, and have been harnessed therapeutically to treat type 2 diabetes and obesity. Our understanding of the enteroendocrine axis arises largely from animal studies, but intestinal organoid models make it possible to identify, genetically modify and purify human enteroendocrine cells (EECs). This study aimed to map human EECs using single-cell RNA sequencing.
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