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

Foley, Stephen, Garsed, Klara, Singh, Gulzar, Duroudier, Nathalie P., Swan, Caroline, Hall, Ian P., Zaitoun, Abed, Bennett, Andrew, Marsden, Charles, Holmes, Geoffrey, Walls, Andrew and Spiller, Robin C. (2011) Impaired uptake of serotonin by platelets from patients with irritable bowel syndrome correlates with duodenal immune activation. Gastroenterology, 140 (5), 1434-1443.e1. (doi:10.1053/j.gastro.2011.01.052). (PMID:21315720)

Abstract

Background & Aims
Patients 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.

Methods
We 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.

Results
Patients with IBS-D or celiac disease had increased numbers of IELs and mast cells compared with HVs (both P < .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 < .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 < .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).

Conclusions
Platelet SERT is reduced in IBS-D and associated with reduced levels of SERT mRNA and duodenal immune activation.

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Contributors

Author: Andrew Walls

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