In vitro and in vivo effect of fluoxetine on the permeability of3H-serotonin across rat intestine

Abstract

The aim of this work was to characterize the mucosal-to-serosal (apical to basolateral; AP-BL) and serosal-to-mucosal (basolateral to apical; BL-AP) transport of serotonin (5-HT) across rat jejunum, ileum, and colon, and to determine the influence of serotonin neuronal transporter inhibitors on this transport. The AP-BL apparent permeability (Papp) of3H-5-HT increased in the order colon = jejunum < ileum, and the BL-AP Pappof3H-5-HT increased in the order colon < jejunum = ileum. In vitro, neither fluoxetine (0.02 or 0.2 µmol/L) nor desipramine (0.4 or 4 µmol/L) had a significant effect upon the AP-BL or BL-AP Pappof3H-5-HT in any of the intestinal regions. However, fluoxetine (0.2 µmol/L) decreased the accumulation of3H-5-HT in the ileum (to 65% of control) in the BL-AP experiments. In vivo, chronic fluoxetine (10 mg/kg daily administered orally for 15 days), as assessed in the ileum, significantly increased (to ±180% of control levels) the BL-AP Pappof3H-5-HT and tended to increase the AP-BL Pappof3H-5-HT. In conclusion, the increase in the Pappof3H-5-HT after chronic administration of fluoxetine suggests that this treatment is able to increase the extracellular concentration of3H-5-HT at the intestinal level.Key words: fluoxetine, serotonin, rat intestine, permeability.