Work

Quetiapine competitively inhibits 5-HT3 receptor-mediated currents in NCB20 neuroblastoma cells

Year: 2024

Type: article

Abstract: The 5-hydroxytryptamine type 3 (5-HT 3 ) receptor, a ligand-gated ion channel, plays a critical role in synaptic transmission.It has been implicated in various neuropsychiatric disorders.This study aimed to elucidate the mechanism by which quetiapine, an atypical antipsychotic, could inhibit 5-HT 3 receptor-mediated currents in NCB20 neuroblastoma cells.Whole-cell patch-clamp recordings were used to study effects of quetiapine on receptor ion channel kinetics and its competitive antagonism.Co-application of quetiapine shifted 5-HT concentration-response curve rightward, significantly increasing the EC 50 without altering the maximal response (E max ), suggesting a competitive inhibition.Quetiapine's IC 50 varied with 5-HT concentration and treatment condition.The IC 50 value of quetiapine was 0.58 μM with 3 μM 5-HT and 25.23 μM with 10 μM 5-HT, indicating an inverse relationship between quetiapine efficacy and agonist concentration.Pretreatment of quetiapine significantly enhanced its inhibitory potency, reducing its IC 50 from 25.23 μM to 0.20 μM.Interaction kinetics experiments revealed an IC 50 of 5.17 μM for an open state of the 5-HT 3 receptor, suggesting weaker affinity during receptor activation.Quetiapine also accelerated receptor deactivation and desensitization, suggesting that it could stabilize the receptor in non-conducting states.Additionally, quetiapine significantly prolonged recovery from desensitization without affecting recovery from deactivation, demonstrating its selective impact on receptor kinetics.Inhibition of the 5-HT 3 receptor by quetiapine was voltage-independent, and quetiapine exhibited no usedependency, further supporting its role as a competitive antagonist.These findings provide insights into inhibitory mechanism of quetiapine on 5-HT 3 receptor and suggest its potential therapeutic implications for modulating serotonergic pathways in neuropsychiatric disorders.

Source: Korean Journal of Physiology and Pharmacology

DOI: 10.4196/kjpp.24.363

Authors: Yong Soo Park, Gyu Min Kim, Ho Jun Sung, Ju Yeong Yu, Ki-Wug Sung

Institution: Catholic University of Korea

Language: English

Topic: Neuroscience and Neuropharmacology Research

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond