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Modulation of GABA and glycine receptors in rat pyramidal hippocampal neurones by 3 alpha 5 beta-pregnanolone derivatives
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SYSNO ASEP 0492171 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Modulation of GABA and glycine receptors in rat pyramidal hippocampal neurones by 3 alpha 5 beta-pregnanolone derivatives Author(s) Bukanova, J. V. (RU)
Solntseva, E. I. (RU)
Kolbaev, S. N. (RU)
Kudová, Eva (UOCHB-X) RID, ORCIDSource Title Neurochemistry International. - : Elsevier - ISSN 0197-0186
Roč. 118, Sep (2018), s. 145-151Number of pages 7 s. Language eng - English Country GB - United Kingdom Keywords neurosteroid ; GABA receptor ; glycine receptor ; pregnanolone ; structure-activity relationship Subject RIV CE - Biochemistry OECD category Biochemistry and molecular biology R&D Projects TE01020028 GA TA ČR - Technology Agency of the Czech Republic (TA ČR) Institutional support UOCHB-X - RVO:61388963 UT WOS 000439674200016 EID SCOPUS 85048388816 DOI 10.1016/j.neuint.2018.06.002 Annotation The ability of pregnanolone glutamate (PA-Glu), pregnanolone hemisuccinate (PA-hSuc) and pregnanolone hemipimelate (PA-hPim), neuroactive steroids with a negative modulatory effect on excitatory N-methyl-D-aspartate receptors, to influence the functional activity of inhibitory gamma-aminobutyric acid and glycine receptors was estimated. The GABA- and glycine-induced chloride currents (I-GABA and I-Gly) were measured in isolated pyramidal neurons of the rat hippocampus using the patch-clamp technique. Compound PA-Glu was found to potentiate I-GABA and to inhibit loy, while PA-hSuc and PA-hPim inhibited both I-GABA and I-Gly. Moreover, PA-Glu, PA-hSuc, and PA-hPim had a greater effect on desensitization than on the peak amplitude of I-Gly. At a high concentration of glycine (500 mu M), the effect of neurosteroids on the peak amplitude of I-Gly disappeared, and the acceleration of desensitization remained. The conversion of PA-Glu into androstane glutamate (AND-Glu), an analogue that lacks the C-17 acetyl moiety, completely eliminated the effects on these receptors. Our results indicate that the C-17 acetyl moiety is crucial for the action on I-GABA and I-Gly. Our results indicate that the pregnanolone derivatives, in contrast to the androstane analogues, modulate I-GABA and I-Gly at low micromolar concentrations and this family of neurosteroids can be useful for future structure-activity relationship studies of the steroid modulation of other receptor types. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2019
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