Uptake of serotonin at the apical and basolateral membranes of human intestinal epithelial (Caco-2) cells occurs through the neuronal serotonin transporter (SERT)

• Type: Article in International Scientific Journal
• Date: 2003

Authors

martel, f (Author) FMUP; monteiro, r (Author) FMUP; lemos, c (Author) Other

Journal

Title: Journal of Pharmacology and Experimental Therapeutics

Vol. 306

Pages: 355-362

ISSN: 0022-3565

Publisher: American Society for Pharmacology and Experimental Therapeutics

Indexing

ISI Web of Knowledge - 63 Citations

Scopus - 62 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-000-G4C

DOI: 10.1124/jpet.103.049668

Abstract (EN): 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 [H-3] 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 greater than or equal to noradrenaline) and tricyclic and non-tricyclic antidepressants (with the following rank order of potency: fluoxetine > desipramine > cocaine > GBR 12909). In contrast, it was not affected by corticosterone (0.01-100 muM) and was only partially inhibited by decynium-22 (0.001-10 muM). Transepithelial apparent permeability (P-app) to [H-3] serotonin in the apical-to-basolateral direction was reduced by desipramine (0.4 muM) and fluoxetine (0.02 muM), and it was not Na+-dependent nor affected by corticosterone (100 muM). Uptake of [H-3] serotonin at the basolateral membrane of Caco-2 cells was Na+ dependent and reduced by desipramine (0.4 muM) and fluoxetine (0.02 muM), and it was not affected by corticosterone (100 muM). The Papp to [H-3] serotonin in the basolateral-to-apical direction was reduced by desipramine (0.4 muM) and fluoxetine (0.02 muM), and it was not affected by Na+ omission or by corticosterone (100 muM). 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8