Modulation of GABA and glycine receptors in rat pyramidal hippocampal neurones by 3 alpha 5 beta-pregnanolone derivatives
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F18%3A00492171" target="_blank" >RIV/61388963:_____/18:00492171 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1016/j.neuint.2018.06.002" target="_blank" >http://dx.doi.org/10.1016/j.neuint.2018.06.002</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.neuint.2018.06.002" target="_blank" >10.1016/j.neuint.2018.06.002</a>
Alternative languages
Result language
angličtina
Original language name
Modulation of GABA and glycine receptors in rat pyramidal hippocampal neurones by 3 alpha 5 beta-pregnanolone derivatives
Original language description
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.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/TE01020028" target="_blank" >TE01020028: Center for Development of Original Drugs</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Neurochemistry International
ISSN
0197-0186
e-ISSN
—
Volume of the periodical
118
Issue of the periodical within the volume
Sep
Country of publishing house
GB - UNITED KINGDOM
Number of pages
7
Pages from-to
145-151
UT code for WoS article
000439674200016
EID of the result in the Scopus database
2-s2.0-85048388816