Neurosteroids as Selective Inhibitors of Glycine Receptor Activity: Structure-Activity Relationship Study on Endogenous Androstanes and Androstenes
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F20%3A00523573" target="_blank" >RIV/61388963:_____/20:00523573 - isvavai.cz</a>
Výsledek na webu
<a href="https://www.frontiersin.org/articles/10.3389/fnmol.2020.00044/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fnmol.2020.00044/full</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3389/fnmol.2020.00044" target="_blank" >10.3389/fnmol.2020.00044</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Neurosteroids as Selective Inhibitors of Glycine Receptor Activity: Structure-Activity Relationship Study on Endogenous Androstanes and Androstenes
Popis výsledku v původním jazyce
The ability of androstane and androstene neurosteroids with modifications at C-17, C-5, and C-3 (compounds 1-9) to influence the functional activity of inhibitory glycine and γ-aminobutyric acid (GABA) receptors was estimated. The glycine- and GABA-induced chloride current (IGly and IGABA) were measured in isolated pyramidal neurons of the rat hippocampus and isolated rat cerebellar Purkinje cells, correspondingly, using the patch-clamp technique. Our results demonstrate that all the nine neurosteroids display similar biological activity, namely, they strongly inhibited IGly and weakly inhibited IGABA. The threshold concentration of neurosteroids inducing effects on IGly was 0.1 μM, and for effects on IGABA was 10–50 μM. Moreover, our compounds accelerated desensitization of the IGly with the IC50 values varying from 0.12 to 0.49 μM and decreased the peak amplitude with IC50 values varying from 16 to 22 μM. Interestingly, our study revealed that only compounds 4 (epiandrosterone) and 8 (dehydroepiandrosterone) were able to cause a significant change in IGABA in 10 μM concentration. Moreover, compounds 3 (testosterone), 5 (epitestosterone), 6 (dihydroandrostenedione), and 9 (etiocholanedione) did not modulate IGABA up to the concentration of 50 μM. Thus, we conclude that compounds 3, 5, 6, and 9 may be identified as selective modulators of IGly. Our results offer new avenues of investigation in the field of drug-like selective modulators of IGly.
Název v anglickém jazyce
Neurosteroids as Selective Inhibitors of Glycine Receptor Activity: Structure-Activity Relationship Study on Endogenous Androstanes and Androstenes
Popis výsledku anglicky
The ability of androstane and androstene neurosteroids with modifications at C-17, C-5, and C-3 (compounds 1-9) to influence the functional activity of inhibitory glycine and γ-aminobutyric acid (GABA) receptors was estimated. The glycine- and GABA-induced chloride current (IGly and IGABA) were measured in isolated pyramidal neurons of the rat hippocampus and isolated rat cerebellar Purkinje cells, correspondingly, using the patch-clamp technique. Our results demonstrate that all the nine neurosteroids display similar biological activity, namely, they strongly inhibited IGly and weakly inhibited IGABA. The threshold concentration of neurosteroids inducing effects on IGly was 0.1 μM, and for effects on IGABA was 10–50 μM. Moreover, our compounds accelerated desensitization of the IGly with the IC50 values varying from 0.12 to 0.49 μM and decreased the peak amplitude with IC50 values varying from 16 to 22 μM. Interestingly, our study revealed that only compounds 4 (epiandrosterone) and 8 (dehydroepiandrosterone) were able to cause a significant change in IGABA in 10 μM concentration. Moreover, compounds 3 (testosterone), 5 (epitestosterone), 6 (dihydroandrostenedione), and 9 (etiocholanedione) did not modulate IGABA up to the concentration of 50 μM. Thus, we conclude that compounds 3, 5, 6, and 9 may be identified as selective modulators of IGly. Our results offer new avenues of investigation in the field of drug-like selective modulators of IGly.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30103 - Neurosciences (including psychophysiology)
Návaznosti výsledku
Projekt
<a href="/cs/project/TN01000013" target="_blank" >TN01000013: Personalizovaná medicína - diagnostika a terapie</a><br>
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2020
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Frontiers in Molecular Neuroscience
ISSN
1662-5099
e-ISSN
—
Svazek periodika
13
Číslo periodika v rámci svazku
Mar 20
Stát vydavatele periodika
CH - Švýcarská konfederace
Počet stran výsledku
11
Strana od-do
44
Kód UT WoS článku
000525630900001
EID výsledku v databázi Scopus
2-s2.0-85083062307