Mucosal serotonin transporter activity reduced in diarrheal IBS, celiac disease
MedWire News: Patients with diarrhea-type irritable bowel syndrome (IBS-D) or celiac disease have reduced platelet serotonin transporter (SERT) function and depressed levels of serotonin transporter mRNA in the small bowel mucosa, according to results from a UK study.
"Our finding that serotonin uptake into platelets is depressed in IBS-D supports the concept that inflammation might depress SERT function generally in IBS-D tissues and hence increase serotonin availability.
"This could contribute to symptoms since serotonin is known to stimulate peristalsis and secretion and to activate intestinal nerves," explain Robin Spiller, from Nottingham University, and colleagues.
In the study, duodenal mucosa biopsies and blood samples were obtained from 20 patients with IBS-D, 20 with untreated celiac disease, and 29 healthy individuals with no history of gastrointestinal disease.
Writing in the journal Gastroenterology, Spiller and colleagues report that they used the mucosal biopsies to measure each participant's SERT mRNA levels, while blood samples were analyzed for the presence of inflammatory cells (intra-epithelial lymphocytes [IELs], mast cells, and enterochromaffin cells), and the extent of platelet uptake of serotonin and H3-paroxetine platelet membrane binding.
The team found that compared with healthy individuals, patients with IBS-D or celiac disease had increased numbers of IELs and mast cells.
SERT mRNA levels inversely correlated with IELs (correlation coefficient -0.72) and thus, were present in lower levels among IBS-D and celiac disease patients than in healthy participants.
An inverse correlation was also observed between platelet uptake of serotonin and platelet membrane binding of paroxetine, with reduced levels of the former and increased levels of the latter measured among IBS-D and celiac disease patients compared with healthy individuals.
Specifically, median platelet membrane binding of paroxetine was 226 versus 109 fmol/mg protein among IBS-D and healthy participants, respectively, while mean platelet uptake of serotonin occurred at respective rates of 17.1 versus 28.3 nmol/min/mg.
Spiller and team explain that the correlation of impaired SERT function with increased platelet paroxetine binding is most likely a compensatory mechanism that occurs because "serotonin is an important component of platelet function which is vital for hemostasis."
They conclude that the findings "should open the way to studies using large numbers of IBS-D patients in which paroxetine binding can be used as a biomarker to subdivide IBS patients and possibly predict their prognosis and response to serotonin receptor antagonists."
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2011
By Lauretta Ihonor