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Verfasst von:Gunn, David [VerfasserIn]   i
 Niesler, Beate [VerfasserIn]   i
Titel:Abnormalities of mucosal serotonin metabolism and 5-HT3 receptor subunit 3C polymorphism in irritable bowel syndrome with diarrhoea predict responsiveness to ondansetron
Verf.angabe:David Gunn, Klara Garsed, Ching Lam, Gulzar Singh, Melanie Lingaya, Verena Wahl, Beate Niesler, Amanda Henry, Ian P. Hall, Peter Whorwell, Robin Spiller
E-Jahr:2019
Jahr:24 July 2019
Umfang:9 S.
Fussnoten:Gesehen am 04.11.2019 ; Im Titel ist die Zahl "3" im Begriff 5-HT3 tiefgestellt
Titel Quelle:Enthalten in: Alimentary pharmacology & therapeutics
Ort Quelle:Oxford : Blackwell Science, 1987
Jahr Quelle:2019
Band/Heft Quelle:50(2019), 5, Seite 538-546
ISSN Quelle:1365-2036
Abstract:Background: Irritable bowel syndrome with diarrhoea (IBS-D) is a common condition, greatly reducing the quality of life with few effective treatment options available. Aim: To report the beneficial response shown in our trial with the 5-hydroyxtryptamine (5-HT) receptor 3 antagonist, ondansetron in IBS-D. Methods: A randomised, placebo-controlled, cross-over trial of 5 weeks of ondansetron versus placebo in 125 patients meeting modified Rome III criteria for IBS-D as previously described. Patients were compared to 21 healthy controls. 5-HT and 5-HIAA were measured in rectal biopsies. Whole gut transit time was assessed using a radio-opaque marker technique. Whole blood DNA was genotyped for an insertion polymorphism in the promoter region of the serotonin transporter gene SLC6A4, as well as single nucleotide polymorphisms (SNPs) of the tryptophan hydroxylase gene TPH1 and 5-HT3 receptor genes HTR3A, C and E. Results: Patients’ biopsies showed significantly higher 5-HIAA levels (2.1 (1.2-4.2) pmol/mg protein vs 1.1 (0.4-1.5) in controls, P < .0001). 39 patients used < 4 mg/d (“super-responders”) while 55 required ≥ 4 mg/d. 5-HT concentrations in rectal biopsies were significantly lower in super-responders (21.3 (17.0-31.8) vs 37.7 (21.4-61.4), P = .0357) and the increase in transit time on ondansetron was significantly greater (15.6 (1.8-31) hours vs 3.9 (−5.1-17.9) hours). Stool consistency responders were more likely to carry the CC genotype of the SNP p.N163K rs6766410 of the HTR3C gene (33% vs 14%, P = .0066). Conclusion: IBS-D patients have significant abnormalities in mucosal 5-HT metabolism. Those with the lowest concentration of 5-HT in rectal biopsies showed the greatest responsiveness to ondansetron.
DOI:doi:10.1111/apt.15420
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1111/apt.15420
 Verlag: https://onlinelibrary.wiley.com/doi/abs/10.1111/apt.15420
 DOI: https://doi.org/10.1111/apt.15420
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1680887807
Verknüpfungen:→ Zeitschrift

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