title: Effect of synthetic steroids on GABAA receptor binding in rat brain.
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.
authors.affiliation: Laboratorio de Neurobiología, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Vuelta de Obligado 2490 (C1428ADN), Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: M
authors.initials: M
authors.lastname: Rey
authors.affiliation: Departamento de Química Orgánica, Unidad de Microanálisis y Métodos Físicos aplicados a Química Orgánica (UMYMFOR-CONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (FCEN-UBA), Pabellón 2, Ciudad Universitaria, Intendente Güiraldes 2160 (C1428EHA), Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: A S
authors.initials: AS
authors.lastname: Veleiro
authors.affiliation: Departamento de Química Orgánica, Unidad de Microanálisis y Métodos Físicos aplicados a Química Orgánica (UMYMFOR-CONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (FCEN-UBA), Pabellón 2, Ciudad Universitaria, Intendente Güiraldes 2160 (C1428EHA), Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: A A
authors.initials: AA
authors.lastname: Ghini
authors.affiliation: Laboratorio de Neurobiología, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Vuelta de Obligado 2490 (C1428ADN), Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: M S
authors.initials: MS
authors.lastname: Kruse
authors.affiliation: Departamento de Química Orgánica, Unidad de Microanálisis y Métodos Físicos aplicados a Química Orgánica (UMYMFOR-CONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (FCEN-UBA), Pabellón 2, Ciudad Universitaria, Intendente Güiraldes 2160 (C1428EHA), Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: G
authors.initials: G
authors.lastname: Burton
authors.affiliation: Laboratorio de Neurobiología, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Vuelta de Obligado 2490 (C1428ADN), 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. Electronic address: hcoirini@ibyme.conicet.gov.ar.
authors.forename: H
authors.initials: H
authors.lastname: Coirini
mesh_terms: D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005445:Flunitrazepam / Q000378:metabolism; D058785:GABA-A Receptor Agonists / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009118:Muscimol / Q000378:metabolism; D011280:Pregnanolone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013462:Sulfur Radioisotopes; D014316:Tritium
chemical_list: C000603444:3-hydroxy-2,19-epoxypregnan-20-one; C000603445:3-hydroxy-6,19-epoxypregn-4-ene-20-one; D019086:Bridged Bicyclo Compounds, Heterocyclic; D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D013462:Sulfur Radioisotopes; D014316:Tritium; D009118:Muscimol; D005445:Flunitrazepam; C037476:tert-butylbicyclophosphorothionate; D011280:Pregnanolone
keywords: GABA(A) receptor; autoradiography; cerebral cortex; hippocampus; neurosteroids; synthetic steroids