Paroxetine suppresses recombinant human P2X7 responses

Purinergic Signalling
Phuong Dao-UngLeanne Stokes

Abstract

P2X7 receptor (P2X7) activity may link inflammation to depressive disorders. Genetic variants of human P2X7 have been linked with major depression and bipolar disorders, and the P2X7 knockout mouse has been shown to exhibit anti-depressive-like behaviour. P2X7 is an ATP-gated ion channel and is a major regulator of the pro-inflammatory cytokine interleukin 1β (IL-1β) secretion from monocytes and microglia. We hypothesised that antidepressants may elicit their mood enhancing effects in part via modulating P2X7 activity and reducing inflammatory responses. In this study, we determined whether common psychoactive drugs could affect recombinant and native human P2X7 responses in vitro. Common antidepressants demonstrated opposing effects on human P2X7-mediated responses; paroxetine inhibited while fluoxetine and clomipramine mildly potentiated ATP-induced dye uptake in HEK-293 cells stably expressing recombinant human P2X7. Paroxetine inhibited dye uptake mediated by human P2X7 in a concentration-dependent manner with an IC(50) of 24 μM and significantly reduces ATP-induced inward currents. We confirmed that trifluoperazine hydrochloride suppressed human P2X7 responses (IC(50) of 6.4 μM). Both paroxetine and trifluoperazine did not...Continue Reading

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Citations

Nov 12, 2017·European Archives of Psychiatry and Clinical Neuroscience·G FondUNKNOWN FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia) group
Jun 9, 2019·International Journal of Molecular Sciences·Deidiane Elisa RibeiroSâmia Joca
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Oct 15, 2021·Immunopharmacology and Immunotoxicology·Malek ZareiSeyed Ali Ziai

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