Pregnane neurosteroids exert opposite effects on GABA and glycine-induced chloride current in isolated rat neurons

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00558551" target="_blank" >RIV/61388963:_____/22:00558551 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1002/hipo.23449" target="_blank" >https://doi.org/10.1002/hipo.23449</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/hipo.23449" target="_blank" >10.1002/hipo.23449</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Pregnane neurosteroids exert opposite effects on GABA and glycine-induced chloride current in isolated rat neurons

Popis výsledku v původním jazyce

The ability of endogenous neurosteroids (NSs) with pregnane skeleton modified at positions C-3 and C-5 to modulate the functional activity of inhibitory glycine receptors (GlyR) and ionotropic ɣ-aminobutyric acid receptors (GABAAR) was estimated. The glycine and GABA-induced chloride current (IGly and IGABA) were measured in isolated pyramidal neurons of the rat hippocampus and in isolated rat cerebellar Purkinje cells, respectively. Our experiments demonstrated that pregnane NSs affected IGABA and IGly in a different manner. At low concentrations (up to 5 μM), tested pregnane NSs increased or did not change the peak amplitude of the IGABA, but reduced the IGly by decreasing the peak amplitude and/or accelerating desensitization. Namely, allopregnanolone (ALLO), epipregnanolone (EPI), pregnanolone (PA), pregnanolone sulfate (PAS) and 5β-dihydroprogesterone (5β-DHP) enhanced the IGABA in Purkinje cells. Dose–response curves plotted in the concentration range from 1 nM to 100 μM were smooth for EPI and 5β-DHP, but bell-shaped for ALLO, PA and PAS. The peak amplitude of the IGly was reduced by PA, PAS, and 5α- and 5β-DHP. In contrast, ALLO, ISO and EPI did not modulate it. Dose–response curves for the inhibition of the IGly peak amplitude were smooth for all active compounds. All NSs accelerated desensitization of the IGly. The dose–response relationship for this effect was smooth for ALLO, PA, PAS and 5β-DHP, but it was U-shaped for EPI, 5α-DHP and ISO. These results, together with our previous results on NSs with androstane skeleton, offer comprehensive overview for understanding the mechanisms of effects of NSs on IGly and IGABA.

Název v anglickém jazyce

Pregnane neurosteroids exert opposite effects on GABA and glycine-induced chloride current in isolated rat neurons

Popis výsledku anglicky

The ability of endogenous neurosteroids (NSs) with pregnane skeleton modified at positions C-3 and C-5 to modulate the functional activity of inhibitory glycine receptors (GlyR) and ionotropic ɣ-aminobutyric acid receptors (GABAAR) was estimated. The glycine and GABA-induced chloride current (IGly and IGABA) were measured in isolated pyramidal neurons of the rat hippocampus and in isolated rat cerebellar Purkinje cells, respectively. Our experiments demonstrated that pregnane NSs affected IGABA and IGly in a different manner. At low concentrations (up to 5 μM), tested pregnane NSs increased or did not change the peak amplitude of the IGABA, but reduced the IGly by decreasing the peak amplitude and/or accelerating desensitization. Namely, allopregnanolone (ALLO), epipregnanolone (EPI), pregnanolone (PA), pregnanolone sulfate (PAS) and 5β-dihydroprogesterone (5β-DHP) enhanced the IGABA in Purkinje cells. Dose–response curves plotted in the concentration range from 1 nM to 100 μM were smooth for EPI and 5β-DHP, but bell-shaped for ALLO, PA and PAS. The peak amplitude of the IGly was reduced by PA, PAS, and 5α- and 5β-DHP. In contrast, ALLO, ISO and EPI did not modulate it. Dose–response curves for the inhibition of the IGly peak amplitude were smooth for all active compounds. All NSs accelerated desensitization of the IGly. The dose–response relationship for this effect was smooth for ALLO, PA, PAS and 5β-DHP, but it was U-shaped for EPI, 5α-DHP and ISO. These results, together with our previous results on NSs with androstane skeleton, offer comprehensive overview for understanding the mechanisms of effects of NSs on IGly and IGABA.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/EF16_025%2F0007444" target="_blank" >EF16_025/0007444: PharmaBrain</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Hippocampus

ISSN

1050-9631

e-ISSN

1098-1063

Svazek periodika

32

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

552-563

Kód UT WoS článku

000811076900001

EID výsledku v databázi Scopus

2-s2.0-85131797034