title: Impaired uptake of serotonin by platelets from patients with irritable bowel syndrome correlates with duodenal immune activation.
abstract: OBJECTIVE
  Patients with irritable bowel syndrome with diarrhea (IBS-D) have increased mucosal serotonin (5-hydroxytryptamine [5-HT]) availability, possibly because immune activation reduces activity of the 5-HT transporter (SERT). We investigated the relationship between mucosal and platelet SERT and immune activation of the duodenal mucosa in patients with IBS-D.
  
  
  METHODS
  We quantified mucosal intraepithelial lymphocytes (IELs), mast cells, and enterochromaffin cells in blood samples, measured levels of SERT messenger RNA (mRNA) in mucosal samples, and assessed platelet uptake of 5-HT and platelet membrane binding of (3)H-paroxetine in samples from 29 healthy volunteers (HVs), 20 patients with IBS-D, and 20 untreated patients with celiac disease.
  
  
  RESULTS
  Patients with IBS-D or celiac disease had increased numbers of IELs and mast cells compared with HVs (both P < .001). Levels of SERT mRNA were reduced in the mucosa of patients with IBS-D or celiac disease and were inversely correlated with numbers of IELs (r = -0.72, P < .0001). Uptake of 5-HT by platelets from patients with IBS-D or celiac disease was reduced (mean, 17.1 ± 3.5 and 28.3 ± 4.1 nmol·min(-1)·mg(-1), respectively) compared with HVs (50.8 ± 8.0 nmol·min(-1)·mg(-1), P < .01 and P = .05, respectively). Binding of paroxetine to membranes of platelets from patients with IBS-D (median [interquartile range], 226 [92-405] fmol/mg protein) was significantly greater than that from HVs (109 [69-175] fmol/mg protein) and correlated inversely with platelet uptake of 5-HT (r = -0.62, P = .03). Tryptase release from incubated biopsy samples was significantly increased in patients with IBS-D (2.2 [0.42-3.5] vs 0.50 [0.25-0.86] ng·mL(-1)·mg(-1) for HVs; P = .03).
  
  
  CONCLUSIONS
  Platelet SERT is reduced in IBS-D and associated with reduced levels of SERT mRNA and duodenal immune activation.
authors.affiliation: National Institute for Health Research Biomedical Research Unit, Nottingham Digestive Diseases Centre, School of Clinical Sciences, Nottingham, England.
authors.forename: Stephen
authors.initials: S
authors.lastname: Foley
authors.forename: Klara
authors.initials: K
authors.lastname: Garsed
authors.forename: Gulzar
authors.initials: G
authors.lastname: Singh
authors.forename: Nathalie P
authors.initials: NP
authors.lastname: Duroudier
authors.forename: Caroline
authors.initials: C
authors.lastname: Swan
authors.forename: Ian P
authors.initials: IP
authors.lastname: Hall
authors.forename: Abed
authors.initials: A
authors.lastname: Zaitoun
authors.forename: Andrew
authors.initials: A
authors.lastname: Bennett
authors.forename: Charles
authors.initials: C
authors.lastname: Marsden
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Holmes
authors.forename: Andrew
authors.initials: A
authors.lastname: Walls
authors.forename: Robin C
authors.initials: RC
authors.lastname: Spiller
mesh_terms: D000328:Adult; D001692:Biological Transport; D001706:Biopsy; D001792:Blood Platelets / Q000378:metabolism*; D004386:Duodenum / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007111:Immunity, Cellular; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D043183:Irritable Bowel Syndrome / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin