title: Ecto-nucleotidase pathway is altered by different treatments with fluoxetine and nortriptyline.
abstract: Depression is one of the most disabling diseases and causes a significant burden to both individual and society. Selective serotonin reuptake inhibitors and tricyclic antidepressants, such as fluoxetine and nortriptyline, respectively, are commonly used in treatment for depression. These antidepressants were tested on cerebral cortex and hippocampal synaptosomes after acute and chronic in vivo and in vitro treatments. In chronic treatment, fluoxetine and nortriptyline decreased ATP hydrolysis (17.8% and 16.3%, respectively) in hippocampus. In cerebral cortex, nortriptyline increased ATP (32.3%), ADP (51.8%), and AMP (59.5%) hydrolysis. However, fluoxetine decreased ATP (25.5%) hydrolysis and increased ADP (80.1%) and AMP (33.3%) hydrolysis. Significant activation of ADP hydrolysis was also observed in acute treatment with nortriptyline (49.8%) in cerebral cortex. However, in hippocampus, ATP (24.7%) and ADP (46.1%) hydrolysis were inhibited. Fluoxetine did not alter enzyme activities in acute treatment for both structures. In addition, there were significant changes in NTPDase activities when fluoxetine and nortriptyline (100, 250, and 500 microM) were tested in vitro. There was no inhibitory effect of fluoxetine and nortriptyline on AMP hydrolysis in cerebral cortex and hippocampus. The findings showed that these antidepressant drugs can affect the ecto-nucleotidase pathway, suggesting that the extracellular adenosine levels could be modulated by these drugs.
authors.affiliation: Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, 90619-900, Porto Alegre, RS, Brazil.
authors.forename: Eduardo Luiz
authors.initials: EL
authors.lastname: Pedrazza
authors.forename: Eduardo Pacheco
authors.initials: EP
authors.lastname: Rico
authors.forename: Mario Roberto
authors.initials: MR
authors.lastname: Senger
authors.forename: Leonardo
authors.initials: L
authors.lastname: Pedrazza
authors.forename: Fernanda Francine
authors.initials: FF
authors.lastname: Zimmermann
authors.forename: João José Freitas
authors.initials: JJ
authors.lastname: Sarkis
authors.forename: Maurício Reis
authors.initials: MR
authors.lastname: Bogo
authors.forename: Carla Denise
authors.initials: CD
authors.lastname: Bonan
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D009661:Nortriptyline / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D007527:Isoenzymes; D005473:Fluoxetine; D012701:Serotonin; D000255:Adenosine Triphosphate; D009661:Nortriptyline; D000251:Adenosine Triphosphatases; C027201:ectoATPase; D000241:Adenosine; D009638:Norepinephrine