Witte AB, D’Amato M, Poulsen SS, Laurent A, Knuhtsen S, Bindslev N, Hansen MB, Schmidt PT. Duodenal epithelial transport in functional dyspepsia: Role of serotonin. World J Gastrointest Pathophysiol 2013; 4(2): 28-36 [PMID: 23755368 DOI: 10.4291/wjgp.v4.i2.28]
Corresponding Author of This Article
Dr. Anne-Barbara Witte, Department of Medicine Solna, Unit of Gastroenterology and Hepatology, Karolinska University Hospital Solna, Karolinska Institute, Solna, SE-171 76 Stockholm, Sweden. anne-barbara.witte@ki.se
Research Domain of This Article
Gastroenterology & Hepatology
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Brief Article
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World J Gastrointest Pathophysiol. May 15, 2013; 4(2): 28-36 Published online May 15, 2013. doi: 10.4291/wjgp.v4.i2.28
Duodenal epithelial transport in functional dyspepsia: Role of serotonin
Anne-Barbara Witte, Mauro D’Amato, Steen Seier Poulsen, Agneta Laurent, Svend Knuhtsen, Niels Bindslev, Mark Berner Hansen, Peter Thelin Schmidt
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
Mauro D’Amato, Agneta Laurent, Department of Biosciences and Nutrition, Karolinska Institute Campus Huddinge, 141 86 Stockholm, Sweden
Steen Seier Poulsen, Niels Bindslev, Department of Biomedical Sciences, Panum Institute, University of Copenhagen, 2200 Copenhagen N, Denmark
Svend Knuhtsen, Mark Berner Hansen, Department of Surgery K, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen NV, Denmark
Mark Berner Hansen, AstraZeneca Research and Development, 431 83 Mölndal, Sweden
Author contributions: The study was designed by Witte AB, Poulsen SS, Bindslev N, Hansen MB and Schmidt PT; Witte AB performed the research with the exception of PCR experiments and the histological staining process and analysed as well as summarized the data; Knuhtsen S performed the endoscopic examinations and assisted in characterizing patients and controls; Bindslev N and Hansen MB provided technical guidance and facilities for biopsy sampling and Ussing experiments; D’Amato M and Laurent A performed the expression studies; Poulsen SS contributed with histological evaluation and guidance in the field; Schmidt PT participated in the data analysis and held overall responsibility for ethical and economic aspects; all authors participated in the revision of the manuscript and approved the final version.
Supported by Grants from the Snedkermester Sophus Jacobsen and Wife Astrid Jacobsen’s Foundation, Else and Mogens Wedell-Wedellsborg Foundation, the Ihre Foundation, the Nanna Svartz Foundation as well as the Swedish Research Council; A Graduate Studentship Award from the Karolinska Faculty Foundation to Witte AB
Correspondence to: Dr. Anne-Barbara Witte, Department of Medicine Solna, Unit of Gastroenterology and Hepatology, Karolinska University Hospital Solna, Karolinska Institute, Solna, SE-171 76 Stockholm, Sweden. anne-barbara.witte@ki.se
Telephone: +46-81-2000990 Fax: +46-85-1775768
Received: December 5, 2012 Revised: February 16, 2013 Accepted: April 13, 2013 Published online: May 15, 2013
Abstract
AIM: 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/cm2 (n = 15) vs 62.5 ± 4.5 mS/cm2 (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).
CONCLUSION: 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.
Core tip: The majority of patients with chronic symptoms from the gastro-duodenal region do not present signs of organic disease during routine examination, which commonly leads to the diagnosis of functional dyspepsia (FD). Our study strongly indicates the involvement of 5-hydroxytryptamine related duodenal mucosal mechanisms in FD pathogenesis. Future studies should further investigate alterations in up- and downstream effects related to HTR3E and HTR7 receptors.
