Pedrazza Eduardo Luiz, Senger Mario Roberto, Pedrazza Leonardo, Zimmermann Fernanda Francine, de Freitas Sarkis João José, Bonan Carla Denise
Laboratório de Neuroquímica e Psicofarmacologia, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul., Avenida Ipiranga, 6681, 90619-900, Porto Alegre, RS, Brazil.
Toxicol In Vitro. 2007 Jun;21(4):671-6. doi: 10.1016/j.tiv.2007.01.006. Epub 2007 Jan 14.
The effects of sertraline, a selective serotonin reuptake inhibitor, and clomipramine, a tricyclic antidepressant, were tested on ecto-nucleotidases from synaptosomes of cerebral cortex and hippocampus of rats. Sertraline and clomipramine (100-500 microM) inhibited NTPDase, but not ecto-5'-nucleotidase activity in both cerebral cortex and hippocampus. In cortical synaptosomes, sertraline inhibited both ATP and ADP hydrolysis in the concentrations tested. The inhibitory effect varied from 21% to 83% for ATP hydrolysis and 48% to 75% for ADP hydrolysis. The inhibition promoted by sertraline in hippocampal synaptosomes varied from 38% to 89% for ATP hydrolysis and 45% to 77% for ADP hydrolysis. A significant inhibition of cortical NTPDase activity by clomipramine was observed in the all concentrations tested (35-72% and 36-87% for ATP and ADP hydrolysis, respectively). Similar effects were observed in hippocampus (29-91% and 48-83% for ATP and ADP hydrolysis, respectively). There was no inhibitory effect of sertraline and clomipramine on AMP hydrolysis in cerebral cortex and hippocampus. Our results have shown that classical antidepressants inhibit the extracellular catabolism of ATP. Therefore, it is possible to suggest that changes induced by antidepressants on bilayer membrane could affect NTPDase activities and consequently, modulating ATP and adenosine levels in the synaptic cleft.
在大鼠大脑皮层和海马体突触体的外切核苷酸酶上测试了选择性5-羟色胺再摄取抑制剂舍曲林和三环类抗抑郁药氯米帕明的作用。舍曲林和氯米帕明（100 - 500微摩尔）抑制大脑皮层和海马体中的NTPD酶，但不抑制外切5'-核苷酸酶活性。在皮层突触体中，舍曲林在所测试的浓度下抑制ATP和ADP的水解。ATP水解的抑制作用在21%至83%之间，ADP水解的抑制作用在48%至75%之间。舍曲林在海马体突触体中对ATP水解的促进抑制作用在38%至89%之间，对ADP水解的促进抑制作用在45%至77%之间。在所有测试浓度下（ATP和ADP水解分别为35 - 72%和36 - 87%）均观察到氯米帕明对皮层NTPD酶活性有显著抑制作用。在海马体中也观察到类似的效果（ATP和ADP水解分别为29 - 91%和48 - 83%）。舍曲林和氯米帕明对大脑皮层和海马体中的AMP水解均无抑制作用。我们的结果表明，经典抗抑郁药抑制ATP的细胞外分解代谢。因此，可以推测抗抑郁药在双层膜上引起的变化可能会影响NTPD酶的活性，从而调节突触间隙中ATP和腺苷的水平。
