Pregnane neurosteroids exert opposite effects on GABA and glycine-induced chloride current in isolated rat neurons
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Pregnane neurosteroids exert opposite effects on GABA and glycine-induced chloride current in isolated rat neurons
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
<a href="/en/project/EF16_025%2F0007444" target="_blank" >EF16_025/0007444: PharmaBrain</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Hippocampus
ISSN
1050-9631
e-ISSN
1098-1063
Volume of the periodical
32
Issue of the periodical within the volume
7
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
552-563
UT code for WoS article
000811076900001
EID of the result in the Scopus database
2-s2.0-85131797034