Pedrazza Eduardo Luiz, Rico Eduardo Pacheco, Senger Mario Roberto, Pedrazza Leonardo, Zimmermann Fernanda Francine, Sarkis João José Freitas, Bogo Maurício Reis, Bonan Carla Denise
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.
Eur J Pharmacol. 2008 Mar 31;583(1):18-25. doi: 10.1016/j.ejphar.2008.01.013. Epub 2008 Jan 26.
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.
抑郁症是最具致残性的疾病之一，给个人和社会都带来了沉重负担。选择性5-羟色胺再摄取抑制剂和三环类抗抑郁药，如氟西汀和去甲替林，分别常用于抑郁症治疗。这些抗抑郁药在急性和慢性体内及体外治疗后，在大脑皮层和海马突触体上进行了测试。在慢性治疗中，氟西汀和去甲替林使海马中的ATP水解分别降低了17.8%和16.3%。在大脑皮层中，去甲替林使ATP（32.3%）、ADP（51.8%）和AMP（59.5%）水解增加。然而，氟西汀使ATP水解降低了25.5%，并使ADP（80.1%）和AMP（33.3%）水解增加。在用去甲替林进行大脑皮层急性治疗时（49.8%），也观察到了ADP水解的显著激活。然而，在海马中，ATP（24.7%）和ADP（46.1%）水解受到抑制。氟西汀在对这两个结构的急性治疗中未改变酶活性。此外，当在体外测试氟西汀和去甲替林（100、250和500微摩尔）时，NTPDase活性有显著变化。氟西汀和去甲替林对大脑皮层和海马中的AMP水解没有抑制作用。研究结果表明，这些抗抑郁药物可影响胞外核苷酸酶途径，提示这些药物可能会调节细胞外腺苷水平。
