title: The enteric serotonergic system is altered in patients with diverticular disease.
abstract: OBJECTIVE
  Disturbances of the enteric serotonergic system have been implicated in several intestinal motility disorders. Patients with diverticular disease (DD) have been reported to exhibit abnormal intestinal motility and innervation patterns. Gene expression profiles of the serotonergic system and distribution of the serotonin type 4 receptor (5HT-4R) were thus studied in patients with DD.
  
  
  METHODS
  Colonic specimens from patients with DD and controls were subjected to quantitative PCR for serotonin receptors 2B, 3A, 4, serotonin transporter and synthesising enzyme tryptophan hydroxylase. Localisation of 5HT-4R was determined by dual-label immunocytochemistry using smooth muscle actin (α-SMA) and pan-neuronal markers (PGP 9.5) and quantitative analysis was carried out. Site-specific gene expression analysis of 5HT-4R was assessed within myenteric ganglia and muscle layers. Correlation of 5HT-4R with muscarinic receptors 2 and 3 (M2R, M3R) messenger RNA expression was determined.
  
  
  RESULTS
  5HT-4R mRNA expression was downregulated in the tunica muscularis and upregulated in the mucosa of patients with DD, whereas the other components of the serotonergic system remained unchanged. 5HT-4R was detected in ganglia and muscle layers, but was decreased in the circular muscle layer and myenteric ganglia of patients with DD. 5HT-4R mRNA expression correlated with M2R/M3R mRNA expression in controls, but not in patients with DD.
  
  
  CONCLUSIONS
  The serotonergic system is compromised in DD. Altered expression of 5HT-4R at mRNA and protein levels may contribute to intestinal motor disturbances reported in patients with DD. The findings support the hypothesis that DD is associated and possibly promoted by an enteric neuromuscular pathology.
authors.affiliation: Institute of Anatomy, Christian-Albrechts-University of Kiel, , Kiel, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Böttner
authors.forename: Martina
authors.initials: M
authors.lastname: Barrenschee
authors.forename: Ines
authors.initials: I
authors.lastname: Hellwig
authors.forename: Jonas
authors.initials: J
authors.lastname: Harde
authors.forename: Jan-Hendrik
authors.initials: JH
authors.lastname: Egberts
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
authors.forename: Dimitri
authors.initials: D
authors.lastname: Zorenkov
authors.forename: Thilo
authors.initials: T
authors.lastname: Wedel
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D012809:Colon, Sigmoid / Q000378:metabolism / Q000503:physiopathology; D004241:Diverticulum, Colon / Q000378:metabolism / Q000503:physiopathology*; D017615:Enteric Nervous System / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism / Q000502:physiology; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism / Q000502:physiology; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism / Q000502:physiology; D059326:Serotonergic Neurons / Q000378:metabolism / Q000502:physiology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism / Q000502:physiology; D059467:Transcriptome / Q000502:physiology; D014365:Tryptophan Hydroxylase / Q000378:metabolism / Q000502:physiology
chemical_list: D044348:Receptors, Serotonin, 5-HT2; D044406:Receptors, Serotonin, 5-HT3; D050486:Serotonin Plasma Membrane Transport Proteins; D044422:Receptors, Serotonin, 5-HT4; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase
keywords: Colonic Diseases; Enteric Nervous System; Enteric Neuromuscular Disease; Real Time Pcr; Serotonin