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Neurosteroids as positive and negative allosteric modulators of ligand-gated ion channels: P2X receptor perspective
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SYSNO ASEP 0572394 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Neurosteroids as positive and negative allosteric modulators of ligand-gated ion channels: P2X receptor perspective Author(s) Sivčev, Sonja (FGU-C) RID, ORCID
Kudová, Eva (UOCHB-X) RID, ORCID
Zemková, Hana (FGU-C) RID, ORCIDNumber of authors 3 Article number 109542 Source Title Neuropharmacology. - : Elsevier - ISSN 0028-3908
Roč. 234, Aug 15 (2023)Number of pages 14 s. Language eng - English Country GB - United Kingdom Keywords P2X receptors ; ion channels ; neurosteroids ; allosteric modulators ; extracellular ATP OECD category Physiology (including cytology) R&D Projects LQ1604 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Limited access Institutional support FGU-C - RVO:67985823 ; UOCHB-X - RVO:61388963 UT WOS 000984666300001 EID SCOPUS 85152443752 DOI https://doi.org/10.1016/j.neuropharm.2023.109542 Annotation Neurosteroids are steroids synthesized de novo in the brain from cholesterol in an independent manner from peripheral steroid sources. The term “neuroactive steroid“ includes all steroids independent of their origin, and newly synthesized analogs of neurosteroids that modify neuronal activities. In vivo application of neuroactive steroids induces potent anxiolytic, antidepressant, anticonvulsant, sedative, analgesic and amnesic effects, mainly through interaction with the γ-aminobutyric acid type-A receptor (GABAAR). However, neuroactive steroids also act as positive or negative allosteric regulators on several ligand-gated channels including N-methyl-d-aspartate receptors (NMDARs), nicotinic acetylcholine receptors (nAChRs) and ATP-gated purinergic P2X receptors. Seven different P2X subunits (P2X1-7) can assemble to form homotrimeric or heterotrimeric ion channels permeable for monovalent cations and calcium. Among them, P2X2, P2X4, and P2X7 are the most abundant within the brain and can be regulated by neurosteroids. Transmembrane domains are necessary for neurosteroid binding, however, no generic motif of amino acids can accurately predict the neurosteroid binding site for any of the ligand-gated ion channels including P2X. Here, we will review what is currently known about the modulation of rat and human P2X by neuroactive steroids and the possible structural determinants underlying neurosteroid-induced potentiation and inhibition of the P2X2 and P2X4 receptors. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2024 Electronic address https://doi.org/10.1016/j.neuropharm.2023.109542
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