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Abstract:

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.

Registro:

Documento: Artículo
Título:Effect of synthetic steroids on GABAA receptor binding in rat brain
Autor:Rey, M.; Veleiro, A.S.; Ghini, A.A.; Kruse, M.S.; Burton, G.; Coirini, H.
Filiación:Laboratorio de Neurobiología, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Vuelta de Obligado 2490 (C1428ADN), Ciudad Autónoma de Buenos Aires, Argentina
Departamento de Química Orgánica, Unidad de Microanalisis y Métodos Físicos aplicados a Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (FCEN-UBA), Pabellón 2, Intendente Güiraldes 2160, Ciudad Autónoma de Buenos Aires, Argentina
Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires Paraguay 2155, Ciudad Autónoma de Buenos Aires, Argentina
Palabras clave: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
Año:2015
Volumen:290
Página de inicio:138
Página de fin:146
DOI: http://dx.doi.org/10.1016/j.neuroscience.2014.12.082
Título revista:Neuroscience
Título revista abreviado:Neuroscience
ISSN:03064522
CODEN:NRSCD
CAS:3alpha hydroxy 5alpha pregnan 20 one, 516-54-1; eltanolone, 128-20-1; flunitrazepam, 1622-62-4; muscimol, 2763-96-4; sulfur, 13981-57-2, 7704-34-9; tritium, 10028-17-8; 3-hydroxy-2,19-epoxypregnan-20-one; 3-hydroxy-6,19-epoxypregn-4-ene-20-one; Bicyclo Compounds, Heterocyclic; Flunitrazepam; GABA-A Receptor Agonists; Muscimol; Pregnanolone; Receptors, GABA-A; Sulfur Radioisotopes; tert-butylbicyclophosphorothionate; Tritium
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03064522_v290_n_p138_Rey

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Citas:

---------- APA ----------
Rey, M., Veleiro, A.S., Ghini, A.A., Kruse, M.S., Burton, G. & Coirini, H. (2015) . Effect of synthetic steroids on GABAA receptor binding in rat brain. Neuroscience, 290, 138-146.
http://dx.doi.org/10.1016/j.neuroscience.2014.12.082
---------- CHICAGO ----------
Rey, M., Veleiro, A.S., Ghini, A.A., Kruse, M.S., Burton, G., Coirini, H. "Effect of synthetic steroids on GABAA receptor binding in rat brain" . Neuroscience 290 (2015) : 138-146.
http://dx.doi.org/10.1016/j.neuroscience.2014.12.082
---------- MLA ----------
Rey, M., Veleiro, A.S., Ghini, A.A., Kruse, M.S., Burton, G., Coirini, H. "Effect of synthetic steroids on GABAA receptor binding in rat brain" . Neuroscience, vol. 290, 2015, pp. 138-146.
http://dx.doi.org/10.1016/j.neuroscience.2014.12.082
---------- VANCOUVER ----------
Rey, M., Veleiro, A.S., Ghini, A.A., Kruse, M.S., Burton, G., Coirini, H. Effect of synthetic steroids on GABAA receptor binding in rat brain. Neuroscience. 2015;290:138-146.
http://dx.doi.org/10.1016/j.neuroscience.2014.12.082