title: In vitro and in vivo effect of fluoxetine on the permeability of 3H-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) of 3H-5-HT increased in the order colon = jejunum < ileum, and the BL-AP Papp of 3H-5-HT increased in the order colon < jejunum = ileum. In vitro, neither fluoxetine (0.02 or 0.2 micromol/L) nor desipramine (0.4 or 4 micromol/L) had a significant effect upon the AP-BL or BL-AP Papp of 3H-5-HT in any of the intestinal regions. However, fluoxetine (0.2 micromol/L) decreased the accumulation of 3H-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 Papp of 3H-5-HT and tended to increase the AP-BL Papp of 3H-5-HT. In conclusion, the increase in the Papp of 3H-5-HT after chronic administration of fluoxetine suggests that this treatment is able to increase the extracellular concentration of 3H-5-HT at the intestinal level.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Porto, Portugal. fmartel@med.up.pt
authors.forename: Fátima
authors.initials: F
authors.lastname: Martel
authors.forename: Rosário
authors.initials: R
authors.lastname: Monteiro
authors.forename: Clara
authors.initials: C
authors.lastname: Lemos
authors.forename: M A
authors.initials: MA
authors.lastname: Vieira-Coelho
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D005473:Fluoxetine / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D014316:Tritium / Q000378:metabolism
chemical_list: D005473:Fluoxetine; D014316:Tritium; D012701:Serotonin