Effect of synthetic steroids on GABAA receptor binding in rat brain

Neuroactive steroids, like allopregnanolone (A) and pregnanolone (P), bind to specifics sites on the GABAA receptor complex and modulate receptor function. They are capable to inhibit or stimulate the binding of GABAA receptor-specific ligands, like t-butyl-bicyclophosphorothionate, flunitrazepam an...

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Autores principales:	Rey, Mariana, Veleiro, Adriana Silvia, Ghini, Alberto Antonio, Burton, Gerardo, Coirini, Héctor
Publicado:	2015
Materias:	Autoradiography Cerebral cortex GABAA receptor Hippocampus Neurosteroids Synthetic steroids 3alpha hydroxy 2beta, 19 epoxy 5alpha pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 3alpha hydroxy 6,19 epoxypregn 4 ene 20 one 4 aminobutyric acid A receptor eltanolone steroid unclassified drug 3-hydroxy-2,19-epoxypregnan-20-one 3-hydroxy-6,19-epoxypregn-4-ene-20-one 4 aminobutyric acid A receptor stimulating agent flunitrazepam fused heterocyclic rings muscimol protein binding sulfur tert-butylbicyclophosphorothionate tritium animal experiment animal tissue Article autoradiography brain cortex brain radiography central nervous system controlled study drug activity drug brain level drug receptor binding drug structure hippocampus in vitro study male neuroimaging nonhuman rat stratum radiatum synaptosome analogs and derivatives animal binding competition chemistry drug effects metabolism Sprague Dawley rat Animals Bicyclo Compounds, Heterocyclic Binding, Competitive Cerebral Cortex Flunitrazepam GABA-A Receptor Agonists Male Muscimol Pregnanolone Protein Binding Rats, Sprague-Dawley Receptors, GABA-A Sulfur Radioisotopes Tritium
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03064522_v290_n_p138_Rey http://hdl.handle.net/20.500.12110/paper_03064522_v290_n_p138_Rey
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_03064522_v290_n_p138_Rey
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spelling	paper:paper_03064522_v290_n_p138_Rey2023-06-08T15:31:18Z Effect of synthetic steroids on GABAA receptor binding in rat brain Rey, Mariana Veleiro, Adriana Silvia Ghini, Alberto Antonio Burton, Gerardo Coirini, Héctor Autoradiography Cerebral cortex GABAA receptor Hippocampus Neurosteroids Synthetic steroids 3alpha hydroxy 2beta, 19 epoxy 5alpha pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 3alpha hydroxy 6,19 epoxypregn 4 ene 20 one 4 aminobutyric acid A receptor eltanolone steroid unclassified drug 3-hydroxy-2,19-epoxypregnan-20-one 3-hydroxy-6,19-epoxypregn-4-ene-20-one 4 aminobutyric acid A receptor 4 aminobutyric acid A receptor stimulating agent eltanolone flunitrazepam fused heterocyclic rings muscimol protein binding sulfur tert-butylbicyclophosphorothionate tritium animal experiment animal tissue Article autoradiography brain cortex brain radiography central nervous system controlled study drug activity drug brain level drug receptor binding drug structure hippocampus in vitro study male neuroimaging nonhuman rat stratum radiatum synaptosome analogs and derivatives animal binding competition brain cortex chemistry drug effects hippocampus metabolism Sprague Dawley rat Animals Autoradiography Bicyclo Compounds, Heterocyclic Binding, Competitive Cerebral Cortex Flunitrazepam GABA-A Receptor Agonists Hippocampus Male Muscimol Pregnanolone Protein Binding Rats, Sprague-Dawley Receptors, GABA-A Sulfur Radioisotopes Tritium Neuroactive steroids, like allopregnanolone (A) and pregnanolone (P), bind to specifics sites on the GABAA receptor complex and modulate receptor function. They are capable to inhibit or stimulate the binding of GABAA receptor-specific ligands, like t-butyl-bicyclophosphorothionate, flunitrazepam and muscimol. We have previously characterized a set of oxygen-bridged synthetic steroids (SS) analogs to A or P using synaptosomes. Considering that the subunit composition of the GABAA receptor throughout the central nervous system affects the magnitude of the modulation of the GABAA receptor by NAS, we evaluated the action of two selected SS, in brain sections containing the cerebral cortex (CC) and hippocampus (HC) using quantitative receptor autoradiography. Both SS affected the binding of the three ligands in a similar way to A and P, with some differences on certain CC layers according to the ligand used. One of the SS, the 3α-hydroxy-6,19-epoxypregn-4-ene-20-one (compound 5), behaved similarly to the natural neuroactive steroids. However, significant differences with compound 5 were observed on the HC CA2 region, making it steroid suitable for a specific action. Those differences may be related to structural conformation of the SS and the subunits' composition present on the receptor complex. © 2015 IBRO. Fil:Rey, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Veleiro, A.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Ghini, A.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Burton, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Coirini, H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2015 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03064522_v290_n_p138_Rey http://hdl.handle.net/20.500.12110/paper_03064522_v290_n_p138_Rey
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Autoradiography Cerebral cortex GABAA receptor Hippocampus Neurosteroids Synthetic steroids 3alpha hydroxy 2beta, 19 epoxy 5alpha pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 3alpha hydroxy 6,19 epoxypregn 4 ene 20 one 4 aminobutyric acid A receptor eltanolone steroid unclassified drug 3-hydroxy-2,19-epoxypregnan-20-one 3-hydroxy-6,19-epoxypregn-4-ene-20-one 4 aminobutyric acid A receptor 4 aminobutyric acid A receptor stimulating agent eltanolone flunitrazepam fused heterocyclic rings muscimol protein binding sulfur tert-butylbicyclophosphorothionate tritium animal experiment animal tissue Article autoradiography brain cortex brain radiography central nervous system controlled study drug activity drug brain level drug receptor binding drug structure hippocampus in vitro study male neuroimaging nonhuman rat stratum radiatum synaptosome analogs and derivatives animal binding competition brain cortex chemistry drug effects hippocampus metabolism Sprague Dawley rat Animals Autoradiography Bicyclo Compounds, Heterocyclic Binding, Competitive Cerebral Cortex Flunitrazepam GABA-A Receptor Agonists Hippocampus Male Muscimol Pregnanolone Protein Binding Rats, Sprague-Dawley Receptors, GABA-A Sulfur Radioisotopes Tritium
spellingShingle	Autoradiography Cerebral cortex GABAA receptor Hippocampus Neurosteroids Synthetic steroids 3alpha hydroxy 2beta, 19 epoxy 5alpha pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 3alpha hydroxy 6,19 epoxypregn 4 ene 20 one 4 aminobutyric acid A receptor eltanolone steroid unclassified drug 3-hydroxy-2,19-epoxypregnan-20-one 3-hydroxy-6,19-epoxypregn-4-ene-20-one 4 aminobutyric acid A receptor 4 aminobutyric acid A receptor stimulating agent eltanolone flunitrazepam fused heterocyclic rings muscimol protein binding sulfur tert-butylbicyclophosphorothionate tritium animal experiment animal tissue Article autoradiography brain cortex brain radiography central nervous system controlled study drug activity drug brain level drug receptor binding drug structure hippocampus in vitro study male neuroimaging nonhuman rat stratum radiatum synaptosome analogs and derivatives animal binding competition brain cortex chemistry drug effects hippocampus metabolism Sprague Dawley rat Animals Autoradiography Bicyclo Compounds, Heterocyclic Binding, Competitive Cerebral Cortex Flunitrazepam GABA-A Receptor Agonists Hippocampus Male Muscimol Pregnanolone Protein Binding Rats, Sprague-Dawley Receptors, GABA-A Sulfur Radioisotopes Tritium Rey, Mariana Veleiro, Adriana Silvia Ghini, Alberto Antonio Burton, Gerardo Coirini, Héctor Effect of synthetic steroids on GABAA receptor binding in rat brain
topic_facet	Autoradiography Cerebral cortex GABAA receptor Hippocampus Neurosteroids Synthetic steroids 3alpha hydroxy 2beta, 19 epoxy 5alpha pregnan 20 one 3alpha hydroxy 5alpha pregnan 20 one 3alpha hydroxy 6,19 epoxypregn 4 ene 20 one 4 aminobutyric acid A receptor eltanolone steroid unclassified drug 3-hydroxy-2,19-epoxypregnan-20-one 3-hydroxy-6,19-epoxypregn-4-ene-20-one 4 aminobutyric acid A receptor 4 aminobutyric acid A receptor stimulating agent eltanolone flunitrazepam fused heterocyclic rings muscimol protein binding sulfur tert-butylbicyclophosphorothionate tritium animal experiment animal tissue Article autoradiography brain cortex brain radiography central nervous system controlled study drug activity drug brain level drug receptor binding drug structure hippocampus in vitro study male neuroimaging nonhuman rat stratum radiatum synaptosome analogs and derivatives animal binding competition brain cortex chemistry drug effects hippocampus metabolism Sprague Dawley rat Animals Autoradiography Bicyclo Compounds, Heterocyclic Binding, Competitive Cerebral Cortex Flunitrazepam GABA-A Receptor Agonists Hippocampus Male Muscimol Pregnanolone Protein Binding Rats, Sprague-Dawley Receptors, GABA-A Sulfur Radioisotopes Tritium
description	Neuroactive steroids, like allopregnanolone (A) and pregnanolone (P), bind to specifics sites on the GABAA receptor complex and modulate receptor function. They are capable to inhibit or stimulate the binding of GABAA receptor-specific ligands, like t-butyl-bicyclophosphorothionate, flunitrazepam and muscimol. We have previously characterized a set of oxygen-bridged synthetic steroids (SS) analogs to A or P using synaptosomes. Considering that the subunit composition of the GABAA receptor throughout the central nervous system affects the magnitude of the modulation of the GABAA receptor by NAS, we evaluated the action of two selected SS, in brain sections containing the cerebral cortex (CC) and hippocampus (HC) using quantitative receptor autoradiography. Both SS affected the binding of the three ligands in a similar way to A and P, with some differences on certain CC layers according to the ligand used. One of the SS, the 3α-hydroxy-6,19-epoxypregn-4-ene-20-one (compound 5), behaved similarly to the natural neuroactive steroids. However, significant differences with compound 5 were observed on the HC CA2 region, making it steroid suitable for a specific action. Those differences may be related to structural conformation of the SS and the subunits' composition present on the receptor complex. © 2015 IBRO.
author	Rey, Mariana Veleiro, Adriana Silvia Ghini, Alberto Antonio Burton, Gerardo Coirini, Héctor
author_facet	Rey, Mariana Veleiro, Adriana Silvia Ghini, Alberto Antonio Burton, Gerardo Coirini, Héctor
author_sort	Rey, Mariana
title	Effect of synthetic steroids on GABAA receptor binding in rat brain
title_short	Effect of synthetic steroids on GABAA receptor binding in rat brain
title_full	Effect of synthetic steroids on GABAA receptor binding in rat brain
title_fullStr	Effect of synthetic steroids on GABAA receptor binding in rat brain
title_full_unstemmed	Effect of synthetic steroids on GABAA receptor binding in rat brain
title_sort	effect of synthetic steroids on gabaa receptor binding in rat brain
publishDate	2015
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03064522_v290_n_p138_Rey http://hdl.handle.net/20.500.12110/paper_03064522_v290_n_p138_Rey
work_keys_str_mv	AT reymariana effectofsyntheticsteroidsongabaareceptorbindinginratbrain AT veleiroadrianasilvia effectofsyntheticsteroidsongabaareceptorbindinginratbrain AT ghinialbertoantonio effectofsyntheticsteroidsongabaareceptorbindinginratbrain AT burtongerardo effectofsyntheticsteroidsongabaareceptorbindinginratbrain AT coirinihector effectofsyntheticsteroidsongabaareceptorbindinginratbrain
_version_	1768546209787543552

Effect of synthetic steroids on GABAA receptor binding in rat brain

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