دورية أكاديمية
أعرض في EDS

Effect of resolvins on sensitisation of TRPV1 and visceral hypersensitivity in IBS.

التفاصيل البيبلوغرافية
العنوان: Effect of resolvins on sensitisation of TRPV1 and visceral hypersensitivity in IBS.
المؤلفون: Perna E; Center of Intestinal Neuro-Immune Interaction, Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium., Aguilera-Lizarraga J; Center of Intestinal Neuro-Immune Interaction, Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium., Florens MV; Center of Intestinal Neuro-Immune Interaction, Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium., Jain P; Center of Intestinal Neuro-Immune Interaction, Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium., Theofanous SA; Center of Intestinal Neuro-Immune Interaction, Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium., Hanning N; Laboratory of Experimental Medicine and Pediatrics (LEMP) and Infla-Med, research consortium of excellence, University of Antwerp, Antwerp, Belgium., De Man JG; Laboratory of Experimental Medicine and Pediatrics (LEMP) and Infla-Med, research consortium of excellence, University of Antwerp, Antwerp, Belgium., Berg M; Laboratory of Experimental Medicine and Pediatrics (LEMP) and Infla-Med, research consortium of excellence, University of Antwerp, Antwerp, Belgium., De Winter B; Laboratory of Experimental Medicine and Pediatrics (LEMP) and Infla-Med, research consortium of excellence, University of Antwerp, Antwerp, Belgium., Alpizar YA; BIOMED, UHasselt, Hasselt, Limburg, Belgium., Talavera K; Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, VIB Center for Brain & Disease Research, Leuven, Belgium., Vanden Berghe P; Laboratory for Enteric Neuroscience, Translational Research Center for Gastrointestinal (TARGID), Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium., Wouters M; Center of Intestinal Neuro-Immune Interaction, Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium., Boeckxstaens G; Center of Intestinal Neuro-Immune Interaction, Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium guy.boeckxstaens@kuleuven.be.
المصدر: Gut [Gut] 2021 Jul; Vol. 70 (7), pp. 1275-1286. Date of Electronic Publication: 2020 Oct 06.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: British Medical Assn Country of Publication: England NLM ID: 2985108R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1468-3288 (Electronic) Linking ISSN: 00175749 NLM ISO Abbreviation: Gut Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London, British Medical Assn.
مواضيع طبية MeSH: Hypersensitivity/*drug therapy , Irritable Bowel Syndrome/*metabolism , Receptors, Cannabinoid/*metabolism , TRPV Cation Channels/*metabolism, Adult ; Animals ; Capsaicin/pharmacology ; Disease Models, Animal ; Docosahexaenoic Acids/pharmacology ; Eicosapentaenoic Acid/analogs & derivatives ; Eicosapentaenoic Acid/pharmacology ; Enterobacteriaceae Infections/complications ; Female ; Ganglia, Spinal ; Histamine ; Humans ; Hypersensitivity/etiology ; Hypersensitivity/metabolism ; Inflammation/chemically induced ; Inflammation/complications ; Irritable Bowel Syndrome/drug therapy ; Male ; Mice ; Middle Aged ; Neurons/metabolism ; Rats
مستخلص: Objective: Resolvins (RvD1, RvD2 and RvE1) are endogenous anti-inflammatory lipid mediators that display potent analgesic properties in somatic pain by modulating transient receptor potential vanilloid 1 (TRPV1) activation. To what extent these molecules could also have a beneficial effect on TRPV1 sensitisation and visceral hypersensitivity (VHS), mechanisms involved in IBS, remains unknown.
Design: The effect of RvD1, RvD2 and RvE1 on TRPV1 activation and sensitisation by histamine or IBS supernatants was assessed on murine dorsal root ganglion (DRG) neurons using live Ca 2+ imaging. Based on the results obtained in vitro, we further studied the effect of RvD2 in vivo using a murine model of post-infectious IBS and a rat model of post-inflammatory VHS. Finally, we also tested the effect of RvD2 on submucosal neurons in rectal biopsies of patients with IBS.
Results: RvD1, RvD2 and RvE1 prevented histamine-induced TRPV1 sensitisation in DRG neurons at doses devoid of an analgesic effect. Of note, RvD2 also reversed TRPV1 sensitisation by histamine and IBS supernatant. This effect was blocked by the G protein receptor 18 (GPR18) antagonist O-1918 (3-30 µM) and by pertussis toxin. In addition, RvD2 reduced the capsaicin-induced Ca 2+ response of rectal submucosal neurons of patients with IBS. Finally, treatment with RvD2 normalised pain responses to colorectal distention in both preclinical models of VHS.
Conclusions: Our data suggest that RvD2 and GPR18 agonists may represent interesting novel compounds to be further evaluated as treatment for IBS.
Competing Interests: Competing interests: None declared.
(© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)
فهرسة مساهمة: Keywords: ION channels; abdominal pain; irritable bowel syndrome; neurogastroenterology; visceral hypersensitivity
المشرفين على المادة: 0 (GPR18 protein, rat)
0 (Receptors, Cannabinoid)
0 (TRPV Cation Channels)
0 (TRPV1 protein, human)
0 (TRPV1 protein, mouse)
0 (Trpv1 protein, rat)
0 (resolvin D1)
0 (resolvin D2)
0 (resolvin D5)
25167-62-8 (Docosahexaenoic Acids)
820484N8I3 (Histamine)
AAN7QOV9EA (Eicosapentaenoic Acid)
GND3JH08JA (5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid)
S07O44R1ZM (Capsaicin)
تواريخ الأحداث: Date Created: 20201007 Date Completed: 20220110 Latest Revision: 20220110
رمز التحديث: 20221213
DOI: 10.1136/gutjnl-2020-321530
PMID: 33023902
قاعدة البيانات: MEDLINE
الوصف
تدمد:1468-3288
DOI:10.1136/gutjnl-2020-321530