Fluoxetine and nortriptyline affect NTPDase and 5'-nucleotidase activities in rat blood serum.
Depression is a serious condition associated with considerable morbidity and mortality. Selective serotonin reuptake inhibitors and tricyclic antidepressants, such as fluoxetine and nortriptyline, respectively, were commonly used in treatment for depression. Selective serotonin reuptake inhibitors have been associated with increased risk of bleeding complications, possibly as a result of inhibition of platelet aggregation. ATP, ADP and adenosine are signaling molecules in the vascular system and nucleotidases activities are considered an important thromboregulatory system which functions in the maintenance of blood fluidity. Therefore, here we investigate the effect of in vivo (acute and chronic) and in vitro treatments with the antidepressant drugs on nucleotidases activities in rat blood serum. In acute treatment, nortriptyline decreased ATP hydrolysis (41%), but not altered ADP and AMP hydrolysis. In contrast, fluoxetine did not alter NTPDase and ecto-5'-nucleotidase activities. A significant inhibition of ATP, ADP, and AMP hydrolysis were observed in chronic treatment with fluoxetine (60%, 32%, and 42% for ATP, ADP, and AMP hydrolysis, respectively). Similar effects were shown in chronic treatment with nortriptyline (37%, 41%, and 30% for ATP, ADP, and AMP hydrolysis, respectively). In addition, there were no significant changes in NTPDase and ecto-5'-nucleotidase activities when fluoxetine and nortriptyline (100, 250, and 500 microM) were tested in vitro. Our results have shown that fluoxetine and nortriptyline changed the nucleotide catabolism, suggesting that homeostasis of vascular system can be altered by antidepressant treatments.
Pedrazza
Eduardo Luiz
EL
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.
Senger
Mario Roberto
MR
Rico
Eduardo Pacheco
EP
Zimmermann
Fernanda Francine
FF
Pedrazza
Leonardo
L
de Freitas Sarkis
João José
JJ
Bonan
Carla Denise
CD
D015720:5'-Nucleotidase / Q000097:blood* / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009661:Nortriptyline / Q000008:administration & dosage / Q000494:pharmacology*; D043583:Nucleoside-Triphosphatase / Q000097:blood* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000928:Antidepressive Agents; D005473:Fluoxetine; D009661:Nortriptyline; D015720:5'-Nucleotidase; D043583:Nucleoside-Triphosphatase