Rapid communicationMolecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome 1 ☆,
Section snippets
Acquisition of human tissue
Human colonic tissue samples were obtained from individuals who met diagnostic criteria for one of the following groups: healthy control (n = 34), UC (n = 22), IBS-D (n = 15), and IBS-C (n = 16). Patients qualifying for either of the 2 IBS groups had to meet Rome II criteria.14 Endoscopic examination and histopathologic biopsy evaluation of the colonic mucosa was used to verify the diagnosis of patients in the UC group. Demographic information is shown in Table 1.
Healthy controls provided
5-HT content
Colonic mucosal 5-HT concentrations in UC, IBS-C, and IBS-D specimens were all significantly lower than those in specimens from healthy controls (Figure 1A). The reduced mucosal 5-HT concentrations in biopsy specimens from subjects with UC, IBS-C, and IBS-D did not differ significantly from one another. When the UC group was divided into severe (histopathologic score of 3) and nonsevere (histopathologic score of 0–2) subgroups, each subgroup had significantly lower 5-HT content than controls;
Discussion
Despite markedly different pathophysiologies, IBS and UC share many clinical features, including diarrhea, constipation, and abdominal discomfort. Because 5-HT initiates motor, secretory, and sensory reflexes in the gut, these symptoms may stem from similar alterations in serotonergic signaling. The objective of this investigation was to determine whether UC and/or IBS are associated with alterations in 5-HT signaling. In the intestinal mucosa, efficient 5-HT signaling involves a number of
References (21)
- et al.
Serotonin content and argentaffin and Paneth cell changes in ulcerative colitis
Gastroenterology
(1962) Roles played by 5-hydroxytryptamine in the physiology of the bowel
Aliment Pharmacol Ther
(1999)Serotonergic modulation of visceral sensationlower gut
Gut
(2002)- et al.
Serotonergic modulation of visceral sensationupper gastrointestinal tract
Gut
(2002) - et al.
Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporterabnormal intestinal motility and the expression of cation transporters
J Neurosci
(2001) - et al.
Guinea pig 5-HT transportercloning, expression, distribution, and function in intestinal sensory reception
Am J Physiol
(1998) - et al.
Localization and function of a 5-HT transporter in crypt epithelia of the gastrointestinal tract
J Neurosci
(1996) - et al.
Serotonin availability is increased in mucosa of guinea pigs with TNBS-induced colitis
Am J Physiol Gastrointest Liver Physiol
(2003) - et al.
Distribution of 5-OH tryptamine (serotonin) in ulcerative colitis
Proc R Soc Med
(1970) - et al.
Impaired synthesis or cellular storage of norepinephrine, dopamine, and 5-hydroxytryptamine in human inflammatory bowel disease
Dig Dis Sci
(2002)
Cited by (672)
5-HT induces regulatory B cells in fighting against inflammation-driven ulcerative colitis
2023, International Immunopharmacology
- ☆
Supported by grants from Novartis Pharmaceuticals Corp. (to G.M.M./P.L.M. and M.D.G.); National Institutes of Health grants DK62267 (to G.M.M.), F32DK60382 (to D.R.L.), and NS12969 (to M.D.G.) and P20 RR-016435 from the COBRE program of the National Center for Research Resources; and a grant from the Crohn’s and Colitis Foundation of Canada (to K.A.S. and G.M.M.). K.A.S. is an Alberta Heritage Foundation for Medical Research Medical Scientist.
- 1
The authors thank Ciara Bannon, Dr. Eric Newton, and Matthew Salter for technical assistance; Drs. Neil Hyman, James Vecchio, Nicholas Ferrentino, Richard Zubaric, and Doris Strader for their assistance in acquiring tissue samples; and Dr. Randy Blakely of Vanderbilt University for providing antibodies directed against SERT.