Serotonin signaling in diverticular disease.
Diverticulosis is extremely common in Western societies and is associated with complications in up to 15%of cases. Altered motility is an important feature of the pathogenesis of diverticular disease, and serotonin (5-HT) release is a primary trigger of gut motility. This study aims to determine whether colonic 5-HT signaling is altered in patients with diverticulosis or diverticulitis, and whether differences in serotonin signaling may distinguish patients with asymptomatic diverticulosis from those who develop disease specific complications. Sigmoid colon biopsies were obtained from healthy control subjects, individuals with asymptomatic diverticulosis, and those with a history of CT-proven diverticulitis within the preceding 6 months. The key elements of 5-HT signaling including content, release, and 5-HT transporter (SERT) expression were analyzed. A significant decrease in SERT transcript levels was present in the mucosa of patients with a history of diverticulitis when compared with controls, but not in those with asymptomatic diverticulosis. Mucosal 5-HT content, enterochromaffin (EC) cell numbers, and TpH-1 mRNA levels were comparable amongst the groups, as were basal and stimulated 5-HT release. Alterations in 5-HT signaling do not appear to be responsible for the development of diverticula. However, patients with a recent history of acute diverticulitis have a significant attenuation in SERT expression and function, likely secondary to previous inflammation. Our findings may explain the persistent symptoms of pain and altered motility so often observed in patients with diverticulitis long after recovery from the acute inflammatory response.
Costedio
Meagan M
MM
Department of Surgery, University of Vermont College of Medicine, Burlington, VT 05405, USA.
Coates
Matthew D
MD
Danielson
Amy B
AB
Buttolph
Thomas R
TR
Blaszyk
Hagen J
HJ
Mawe
Gary M
GM
Hyman
Neil H
NH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D012809:Colon, Sigmoid; D004239:Diverticulitis, Colonic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*
D012333:RNA, Messenger; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin