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

L.M Zanatta,A.T.S Wyse,C.A Netto,G.R.R.S Silva,A.I Zugno,S.V.T Barros,F.C Nascimento

doi:10.1590/s0100-879x2001001000005

L.M Zanatta, A.T.S Wyse + Show 5 more

Open Access

https://doi.org/10.1590/s0100-879x2001001000005

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Abstract

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.

Highlights

Na+,K+-ATPase is the enzyme responsible for the active transport of sodium and potassium ions in the nervous system, maintaining the ionic gradient necessary for neuronal excitability and regulation of neuronal cell volume. It is present in high concentrations in brain cellular membranes, consuming about 40-50% of the ATP generated in this tissue [1] and its activity is decreased in patients with bipolar affective disorder and other psychiatric disorders [2]
Since a) imipramine and fluoxetine are antidepressant drugs with similar efficacy and with an important role in the therapeutic arsenal for bipolar affective disorder, and b) Na+,K+-ATPase activity seems to be important for noradrenaline and 5-HT reuptake and its activity is decreased in patients with bipolar affective disorder, in the present study we investigated Na+,K+-ATPase activity in the synaptic plasma membrane from cerebral cortex of adult rats submitted to chronic administration of imipramine and fluoxetine
In agreement with a previous study [7], our results showed that imipramine significantly inhibited Na+,K+-ATPase activity in a dose-dependent manner (r = 0.91, P

Summary

Introduction

Na+,K+-ATPase is the enzyme responsible for the active transport of sodium and potassium ions in the nervous system, maintaining the ionic gradient necessary for neuronal excitability and regulation of neuronal cell volume. Since a) imipramine and fluoxetine are antidepressant drugs with similar efficacy and with an important role in the therapeutic arsenal for bipolar affective disorder, and b) Na+,K+-ATPase activity seems to be important for noradrenaline and 5-HT reuptake and its activity is decreased in patients with bipolar affective disorder, in the present study we investigated Na+,K+-ATPase activity in the synaptic plasma membrane from cerebral cortex of adult rats submitted to chronic administration of imipramine and fluoxetine.

Results

Conclusion