Abstract
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 (Papp) 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 Papp 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.
Footnotes
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This work was supported by Fundação para Ciênua e a Tecnologia and Programa Ciência, Tecnologia e Inovação do Quadro Comunitário de Apoio (POCTI/FCB/37278/2001).
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DOI: 10.1124/jpet.103.049668.
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ABBREVIATIONS: EC, enterochromaffin; SERT, serotonin transporter; OCT, organic cation transporter; TEER, transepithelial resistance; Papp, apparent permeability; RT-PCR, reverse transcriptase-polymerase chain reaction; RT, reverse transcriptase; PCR, polymerase chain reaction; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; NAT, noradrenaline transporter; DAT, dopamine transporter; GBR 12909, 1-(2-bis(4-fluorphenyl)-methoxy)-ethyl-4-3-phenyl-propyl)piperazine.
- Received January 28, 2003.
- Accepted April 4, 2003.
- The American Society for Pharmacology and Experimental Therapeutics
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