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GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Uptake of Serotonin at the Apical and Basolateral Membranes of Human Intestinal Epithelial (Caco-2) Cells Occurs through the Neuronal Serotonin Transporter (SERT)

Department of Biochemistry (U-38), Faculty of Medicine, University of Porto, Porto, Portugal

Serotonin plays important physiological functions at the intestinal level. However, nothing is known concerning its inactivation mechanisms in the human intestine. So, the aim of this work was to characterize the uptake of serotonin at the apical and basolateral membranes of human intestinal epithelial (Caco-2) cells. Uptake of [³H]serotonin at the apical membrane of Caco-2 cells was specific and Na⁺-, Cl^–-, and potential-dependent. It was concentration dependently inhibited by several monoamines (with the following rank order of potency: serotonin >> dopamine ≥ noradrenaline) and tricyclic and nontricyclic antidepressants (with the following rank order of potency: fluoxetine > desipramine > cocaine > GBR 12909). In contrast, it was not affected by corticosterone (0.01–100 µM) and was only partially inhibited by decynium-22 (0.001–10 µM). Transepithelial apparent permeability (P_app) to [³H]serotonin in the apical-to-basolateral direction was reduced by desipramine (0.4 µM) and fluoxetine (0.02 µM), and it was not Na⁺-dependent nor affected by corticosterone (100 µM). Uptake of [³H]serotonin at the basolateral membrane of Caco-2 cells was Na⁺-dependent and reduced by desipramine (0.4 µM) and fluoxetine (0.02 µM), and it was not affected by corticosterone (100 µM). The P_app to [³H]serotonin in the basolateral-to-apical direction was reduced by desipramine (0.4 µM) and fluoxetine (0.02 µM), and it was not affected by Na⁺ omission or by corticosterone (100 µM). Reverse transcriptase-polymerase chain reaction indicates that mRNA of the neuronal serotonin transporter (SERT) is present in Caco-2 cells and in human small intestine. In conclusion, these results suggest that human intestinal epithelial Caco-2 cells functionally express SERT, both at their apical and basolateral cell membranes.

Address correspondence to: Dr. F. Martel, Department of Biochemistry, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal. E-mail: fmartel{at}med.up.pt

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