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Corticosteroids as Selective and Effective Modulators of Glycine Receptors
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SYSNO ASEP 0575132 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Corticosteroids as Selective and Effective Modulators of Glycine Receptors Tvůrce(i) Solntseva, E. I. (RU)
Bukanova, J. V. (RU)
Kondratenko, R. (RU)
Kudová, Eva (UOCHB-X) RID, ORCIDZdroj.dok. ACS Chemical Neuroscience. - : American Chemical Society - ISSN 1948-7193
Roč. 14, č. 17 (2023), s. 3132-3142Poč.str. 11 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova GABAA receptor ; glycine receptor ; corticosteroids ; structure-activity relationship study Obor OECD Neurosciences (including psychophysiology CEP LX22NPO5104 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora UOCHB-X - RVO:61388963 UT WOS 001049417000001 EID SCOPUS 85169054920 DOI https://doi.org/10.1021/acschemneuro.3c00287 Anotace The mechanism of the negative impact of corticosteroids on the induction and progress of mental illness remains unclear. In this work, we studied the effects of corticosteroids on the activity of neuronal glycine receptors (GlyR) and GABA-A receptors (GABAAR) by measuring the chloride current induced by the application of GABA (2 or 5 μM) to isolated cerebellar Purkinje cells (IGABA) and by the application of glycine (100 μM) to pyramidal neurons of the rat hippocampus (IGly). It was found that corticosterone, 5α-dihydrodeoxycorticosterone, allotetrahydrocorticosterone, cortisol, and 17α,21-dihydroxypregnenolone were able to accelerate the desensitization of the IGly at physiological concentrations (IC50 values varying from 0.39 to 0.72 μM). Next, cortisone, 11-deoxycortisol, 11-deoxycorticosterone, 5β-dihydrodeoxycorticosterone, and tetrahydrocorticosterone accelerated the desensitization of IGly with IC50 values varying from 10.3 to 15.2 μM. Allotetrahydrocorticosterone and tetrahydrocorticosterone potentiated the IGABA albeit with high EC50 values (18–23 μM). The rest of the steroids had no effect on IGABA in the range of concentrations of 1–100 μM. Finally, our study has suggested a structural relationship of the 3β-hydroxyl group/3-oxo group with the selective modulatory activity on GlyRs in contrast to the 3α-hydroxyl group that is pivotal for GABAARs. In summary, our results suggest that increased GlyR desensitization by corticosteroids may contribute to brain dysfunction under chronic stress and identify corticosteroids for further development as selective modulators of GlyRs. Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Rok sběru 2024 Elektronická adresa https://doi.org/10.1021/acschemneuro.3c00287
Počet záznamů: 1