title: Duodenal epithelial transport in functional dyspepsia: Role of serotonin.
abstract: OBJECTIVE
  To investigate functional duodenal abnormalities in functional dyspepsia (FD) and the role of serotonin (5-hydroxytryptamine, 5-HT) in mucosal ion transport and signalling.
  
  
  METHODS
  Duodenal mucosal biopsies were obtained from 15 patients with FD and 18 healthy controls. Immunohistochemistry was used to study the number of 5-HT-containing cells and real-time polymerase chain reaction for expression of 5-HT receptors 1A, 1B, 2A, 2B, 3A, 3B, 3C, 3D, 3E, 4 and 7, as well as expression of the serotonin re-uptake transporter (SERT) gene SLC6A4 and tryptophan hydroxylase 1 (TPH1). Biopsies were mounted in Ussing chambers for evaluation of basal and 5-HT-stimulated short-circuit current (SCC).
  
  
  RESULTS
  Conductance was lower in FD [42.4 ± 4.7 mS/cm(2) (n = 15) vs 62.5 ± 4.5 mS/cm(2) (n = 18), P = 0.005]. 5-HT induced a dose dependent rise in SCC in both FD (n = 8) and controls (n = 9), the rise was lower in FD (P < 0.001). Mean number of 5-HT stained cells per high power field was the same [34.4 ± 8.4 in FD (n = 15) and 30.4 ± 3.7 in controls (n = 18), P = 0.647]. The following genes were highly expressed: 5-HT receptor HTR3E, HTR4, HTR7, SERT gene (SLC6A4) and TPH1. Differences in expression levels were observed for HTR3E (higher expression in FD, P = 0.008), HTR7 (lower expression in FD, P = 0.027), SLC6A4 (higher expression in FD, P = 0.033) and TPH1 (lower expression in FD, P = 0.031).
  
  
  CONCLUSIONS
  Duodenal ion transport in response to exogenous 5-HT is abnormal in FD patients and associated with high expression of the HTR3E receptor and the serotonin transporter.
authors.affiliation: Anne-Barbara Witte, Peter Thelin Schmidt, Department of Medicine Solna, Unit of Gastroenterology and Hepatology, Karolinska University Hospital Solna, Karolinska Institute, SE-171 76 Stockholm, Sweden.
authors.forename: Anne-Barbara
authors.initials: AB
authors.lastname: Witte
authors.forename: Mauro
authors.initials: M
authors.lastname: D'Amato
authors.forename: Steen Seier
authors.initials: SS
authors.lastname: Poulsen
authors.forename: Agneta
authors.initials: A
authors.lastname: Laurent
authors.forename: Svend
authors.initials: S
authors.lastname: Knuhtsen
authors.forename: Niels
authors.initials: N
authors.lastname: Bindslev
authors.forename: Mark Berner
authors.initials: MB
authors.lastname: Hansen
authors.forename: Peter Thelin
authors.initials: PT
authors.lastname: Schmidt
keywords: Duodenum; Dyspepsia; Epithelium; Gene expression; Ion transport; Serotonin