Corticosteroids as Selective and Effective Modulators of Glycine Receptors
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00575132" target="_blank" >RIV/61388963:_____/23:00575132 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1021/acschemneuro.3c00287" target="_blank" >https://doi.org/10.1021/acschemneuro.3c00287</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acschemneuro.3c00287" target="_blank" >10.1021/acschemneuro.3c00287</a>
Alternative languages
Result language
angličtina
Original language name
Corticosteroids as Selective and Effective Modulators of Glycine Receptors
Original language description
The mechanism of the negative impact of corticosteroids on the induction and progress of mental illness remains unclear. In this work, we studied the effects of corticosteroids on the activity of neuronal glycine receptors (GlyR) and GABA-A receptors (GABAAR) by measuring the chloride current induced by the application of GABA (2 or 5 μM) to isolated cerebellar Purkinje cells (IGABA) and by the application of glycine (100 μM) to pyramidal neurons of the rat hippocampus (IGly). It was found that corticosterone, 5α-dihydrodeoxycorticosterone, allotetrahydrocorticosterone, cortisol, and 17α,21-dihydroxypregnenolone were able to accelerate the desensitization of the IGly at physiological concentrations (IC50 values varying from 0.39 to 0.72 μM). Next, cortisone, 11-deoxycortisol, 11-deoxycorticosterone, 5β-dihydrodeoxycorticosterone, and tetrahydrocorticosterone accelerated the desensitization of IGly with IC50 values varying from 10.3 to 15.2 μM. Allotetrahydrocorticosterone and tetrahydrocorticosterone potentiated the IGABA albeit with high EC50 values (18–23 μM). The rest of the steroids had no effect on IGABA in the range of concentrations of 1–100 μM. Finally, our study has suggested a structural relationship of the 3β-hydroxyl group/3-oxo group with the selective modulatory activity on GlyRs in contrast to the 3α-hydroxyl group that is pivotal for GABAARs. In summary, our results suggest that increased GlyR desensitization by corticosteroids may contribute to brain dysfunction under chronic stress and identify corticosteroids for further development as selective modulators of GlyRs.
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/LX22NPO5104" target="_blank" >LX22NPO5104: National Institute for Research of Metabolic and Cardiovascular Diseases</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
ACS Chemical Neuroscience
ISSN
1948-7193
e-ISSN
1948-7193
Volume of the periodical
14
Issue of the periodical within the volume
17
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
3132-3142
UT code for WoS article
001049417000001
EID of the result in the Scopus database
2-s2.0-85169054920