Sertraline and clomipramine inhibit nucleotide catabolism in rat brain synaptosomes.
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.
Pedrazza
Eduardo Luiz
EL
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.
Senger
Mario Roberto
MR
Pedrazza
Leonardo
L
Zimmermann
Fernanda Francine
FF
de Freitas Sarkis
João José
JJ
Bonan
Carla Denise
CD
D015720:5'-Nucleotidase / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D002997:Clomipramine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009705:Nucleosides / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020280:Sertraline / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D009419:Nerve Tissue Proteins; D009705:Nucleosides; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D015720:5'-Nucleotidase; D002997:Clomipramine; D020280:Sertraline