In vivo and in vitro effect of imipramine and fluoxetine on Na+,K+-ATPase activity in synaptic plasma membranes from the cerebral cortex of rats.
The effects of in vivo chronic treatment and in vitro addition of imipramine, a tricyclic antidepressant, or fluoxetine, a selective serotonin reuptake inhibitor, on the cortical membrane-bound Na+,K+-ATPase activity were studied. Adult Wistar rats received daily intraperitoneal injections of 10 mg/kg of imipramine or fluoxetine for 14 days. Twelve hours after the last injection rats were decapitated and synaptic plasma membranes (SPM) from cerebral cortex were prepared to determine Na+,K+-ATPase activity. There was a significant decrease (10%) in enzyme activity after imipramine but fluoxetine treatment caused a significant increase (27%) in Na+,K+-ATPase activity compared to control (P<0.05, ANOVA; N = 7 for each group). When assayed in vitro, the addition of both drugs to SPM of naive rats caused a dose-dependent decrease in enzyme activity, with the maximal inhibition (60-80%) occurring at 0.5 mM. We suggest that a) imipramine might decrease Na+,K+-ATPase activity by altering membrane fluidity, as previously proposed, and b) stimulation of this enzyme might contribute to the therapeutic efficacy of fluoxetine, since brain Na+,K+-ATPase activity is decreased in bipolar patients.
Zanatta
L M
LM
Departamento de Medicina Interna, Fundação Universidade do Rio Grande, Rio Grande, RS, Brasil.
Nascimento
F C
FC
Barros
S V
SV
Silva
G R
GR
Zugno
A I
AI
Netto
C A
CA
Wyse
A T
AT
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology; D005473:Fluoxetine / Q000494:pharmacology*; D007099:Imipramine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects* / Q000378:metabolism; D013570:Synaptic Membranes / Q000187:drug effects* / Q000201:enzymology
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D005473:Fluoxetine; D007099:Imipramine; D017367:Selective Serotonin Reuptake Inhibitors; D000254:Sodium-Potassium-Exchanging ATPase