Inhibition of kidney potassium channels by fluoxetine: In vivo and in vitro studies

Autores da FMUP

• Maria Augusta Vieira Coelho

  Autor

• Maria De Fátima Moreira Martel

  Autor

Unidades de investigação

• Biomedicina

Abstract

In vitro studies have demonstrated that fluoxetine, a commonly used antidepressant drug, can modulate the activity of K+ channels. In the present study, we investigated the in vivo effect of acute and sub-chronic treatment of rats with fluoxetine on K+ renal transport. Furthermore, OK cells, a kidney epithelial cell line, were used in order to evaluate the in vitro effect of fluoxetine on K+ currents. In the sub-chronic study, fluoxetine was administrated daily (10 mg/kg, p.o.) for 15 days to male adult Wistar rats. In the acute study, rats were given increasing doses of fluoxetine (1, 3, 10, 30 and 50 mg/kg, p.o.) for 24 h. Results from the sub-chronic study show that urinary K+ content (in mmol/L) was markedly reduced in the fluoxetine-treated animals (fluoxetine: 83 +/- 9; control: 131 +/- 10; P < 0.001). K+ fractional renal excretion (in %) was also significantly lower in the fluoxetine group (fluoxetine: 6 +/- 1; control: 13 +/- 2; P < 0.001). No significant changes was observed in creatinine clearance and on renal tubular Na+,K+-ATPase activity. Results obtained from the acute study demonstrate that, after a 24-h administration, fluoxetine produced a dose-dependent decrease in urinary K+, with an ED50 (in mg/kg) of 4.2 (2.8; 5.5) and a maximal effect of 62% reduction. In vitro, fluoxetine produced a concentration-dependent inhibition of K+ currents in OK cells, with an EC50 of 107 (84.8; 129.5) mu M. In conclusion, fluoxetine produces a marked reduction on urinary K+ excretion; this effect constitutes an in vivo evidence for the inhibitory action of fluoxetine on kidney epithelial K+ channels.

Keywords

• fluoxetine; K+ channels; kidney; OK cells