Inhibition of kidney potassium channels by fluoxetine: In vivo and in vitro studies. (26th September 2022)

• Record Type: Journal Article
• Authors: Vieira‐Coelho, Maria A.; Martel, Fátima
• Is Part Of: Fundamental & clinical pharmacology. Volume 37:Number 2(2023)
• Page Start: 226
• Page End: 234
• Publication Date: 2022-09-26
• Subjects: fluoxetine -- K+ channels -- kidney -- OK cells; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/fcp.12833
• Languages: English
• ISSNs: 0767-3981

Abstract

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) μM. 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.