Impaired uptake of serotonin by platelets from patients with irritable bowel syndrome correlates with duodenal immune activation

Abstract

Background &amp; AimsPatients with irritable bowel syndrome with diarrhea (IBS-D) have increased mucosal serotonin (5-hydroxytryptamine [5-HT]) availability, possibly because immune activation reduces activity of the 5-HT transporter (SERT). We investigated the relationship between mucosal and platelet SERT and immune activation of the duodenal mucosa in patients with IBS-D.MethodsWe quantified mucosal intraepithelial lymphocytes (IELs), mast cells, and enterochromaffin cells in blood samples, measured levels of SERT messenger RNA (mRNA) in mucosal samples, and assessed platelet uptake of 5-HT and platelet membrane binding of 3H-paroxetine in samples from 29 healthy volunteers (HVs), 20 patients with IBS-D, and 20 untreated patients with celiac disease.ResultsPatients with IBS-D or celiac disease had increased numbers of IELs and mast cells compared with HVs (both P &lt; .001). Levels of SERT mRNA were reduced in the mucosa of patients with IBS-D or celiac disease and were inversely correlated with numbers of IELs (r = ?0.72, P &lt; .0001). Uptake of 5-HT by platelets from patients with IBS-D or celiac disease was reduced (mean, 17.1 ± 3.5 and 28.3 ± 4.1 nmol • min?1 • mg?1, respectively) compared with HVs (50.8 ± 8.0 nmol • min?1 • mg?1, P &lt; .01 and P = .05, respectively). Binding of paroxetine to membranes of platelets from patients with IBS-D (median [interquartile range], 226 [92–405] fmol/mg protein) was significantly greater than that from HVs (109 [69–175] fmol/mg protein) and correlated inversely with platelet uptake of 5-HT (r = ?0.62, P = .03). Tryptase release from incubated biopsy samples was significantly increased in patients with IBS-D (2.2 [0.42–3.5] vs 0.50 [0.25–0.86] ng • mL?1 • mg?1 for HVs; P = .03).ConclusionsPlatelet SERT is reduced in IBS-D and associated with reduced levels of SERT mRNA and duodenal immune activation.<br/