Duodenal epithelial transport in functional dyspepsia: Role of serotonin

AIM: To investigate functional duodenal abnormalitiesin functional dyspepsia (FD) and the role of serotonin5-hydroxytryptamine (5-HT) in mucosal ion transportand signalling. METHODS: Duodenal mucosal biopsies were obtainedfrom 15 patients with FD and 18 healthy controls. Immunohistochemistrywas used to study the number of5-HT-containing cells and real-time polymerase chainreaction for expression of 5-HT receptors 1A, 1B, 2A,2B, 3A, 3B, 3C, 3D, 3E, 4 and 7, as well as expressionof the serotonin re-uptake transporter (SERT) gene SLC6A4and tryptophan hydroxylase 1 (TPH1). Biopsieswere mounted in Ussing chambers for evaluation ofbasal and 5-HT-stimulated short-circuit current (SCC). RESULTS: Conductance was lower in FD [42.4 ± 4.7mS/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 perhigh 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 receptorHTR 3E, HTR4 , HTR7 , SERT gene (SLC6A4 ) andTPH1 . Differences in expression levels were observedfor HTR3E (higher expression in FD, P = 0.008), HTR7(lower expression in FD, P = 0.027), SLC6A4 (higherexpression in FD, P = 0.033) and TPH1 (lower expressionin FD, P = 0.031). CONCLUSION: Duodenal ion transport in response toexogenous 5-HT is abnormal in FD patients and associatedwith high expression of the HTR3E receptor andthe serotonin transporter.