0575132 - ÚOCHB 2024 RIV US eng J - Článek v odborném periodiku
Solntseva, E. I. - Bukanova, J. V. - Kondratenko, R. - Kudová, Eva
Corticosteroids as Selective and Effective Modulators of Glycine Receptors.
ACS Chemical Neuroscience. Roč. 14, č. 17 (2023), s. 3132-3142. ISSN 1948-7193. E-ISSN 1948-7193
Grant CEP: GA MŠMT(CZ) LX22NPO5104
Institucionální podpora: RVO:61388963
Klíčová slova: GABAA receptor * glycine receptor * corticosteroids * structure-activity relationship study
Obor OECD: Neurosciences (including psychophysiology
Impakt faktor: 5, rok: 2022
Způsob publikování: Open access
https://doi.org/10.1021/acschemneuro.3c00287

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.
Trvalý link: https://hdl.handle.net/11104/0344992