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MUCOSAL BIOLOGY

Function, expression, and characterization of the serotonin transporter in the native human intestine

¹Department of Medicine, University of Illinois at Chicago, ⁴Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois; ²Department of Pathology, University of Virginia Health System, Charlottesville, Virginia; and ³Department of Pathology, University of Chicago, Chicago, Illinois

Submitted 3 August 2007 ; accepted in final form 3 November 2007

The enteric serotonin transporter (SERT) plays a critical role in modulating serotonin availability and thus has been implicated in the pathogenesis of various intestinal disorders. To date, SERT expression and function in the human intestine have not been investigated. Current studies were designed to characterize the function, expression, distribution, and membrane localization of SERT in the native human intestine. Real-time PCR studies showed relatively higher SERT mRNA expression in the human small intestine compared with colon (ileum >> duodenum >> jejunum). Northern blot analysis revealed three mRNA hybridizing species encoding SERT (3.0, 4.9, and 6.8 kb) in the human ileum. Consistent with SERT mRNA expression, SERT immunostaining was mainly detected in the epithelial cells of human duodenal and ileal resected tissues. Notably, SERT expression was localized predominantly to the apical and intracellular compartments and was distributed throughout the crypt-villus axis. Immunoblotting studies detected a prominent protein band (70 kDa) in the ileal apical plasma membrane vesicles (AMVs) isolated from mucosa obtained from organ-donor intestine. Functional studies showed that uptake of [³H]serotonin (150 nM) in human ileal AMVs was 1) significantly increased in the presence of both Na⁺ and Cl^–; 2) inhibited (50%) by the neuronal SERT inhibitor, fluoxetine (10 µM) and by unlabeled 5-HT; and 3) exhibited saturation kinetics indicating the presence of a carrier-mediated process. Our studies demonstrated differential expression of SERT across various regions of the human intestine and provide evidence for the existence of a functional SERT capable of removing intraluminal serotonin in human ileal epithelial cells.

serotonin uptake; serotonin transporter expression