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Title: The GABAA receptor complex in hepatic encephalopathy. Autoradiographic evidence for the presence of elevated levels of a benzodiazepine receptor ligand

Abstract

Autoradiographic analysis was used to examine radioligand binding to benzodiazepine (BZ) and GABAA receptors in the brains of rabbits with hepatic encephalopathy (HE). Thin sections of whole brain from normal rabbits and rabbits with HE were mounted on slides and subdivided into two groups. One group was washed before incubation with radioligand, while the second group was not prewashed. (3H)Flunitrazepam binding to BZ receptors was decreased by 22% to 42% (p less than 0.05) in the cerebral cortex, superior and inferior colliculi, and cerebellum of unwashed sections from rabbits with HE compared to all other groups. The binding of (3H)Ro 15-1788 to unwashed sections from rabbits with HE was reduced by a similar degree (18% to 37%, p less than 0.05) in the cerebral cortex, hippocampus, superior colliculus, and cerebellar cortex. Incubation of sections with the GABA-mimetic muscimol and NaCl produced an additional decrease in (3H)flunitrazepam binding to the cortex and hippocampus (25% to 31%, p less than 0.05) in unwashed HE rabbit brain, but increased radioligand binding (27% to 71%, p less than 0.05) to several regions in control rabbits. No changes in radioligand binding to either GABAA or peripheral benzodiazepine receptors was observed between HE and control rabbitmore » sections. These findings are consistent with previous electrophysiologic and neurochemical observations indicating no significant changes in either the function or density of GABAA or BZ receptors in this model of HE. Further, they indicate that a reversible BZ receptor ligand with agonist properties is present in the brain in HE. This substance may contribute to the enhancement of GABAergic tone observed in this syndrome.« less

Authors:
; ; ; ;  [1]
  1. National Institutes of Health, Bethesda, MD (USA)
Publication Date:
OSTI Identifier:
7138041
Resource Type:
Journal Article
Journal Name:
Neuropsychopharmacology; (USA)
Additional Journal Information:
Journal Volume: 3:1; Journal ID: ISSN 0893-133X
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; AMINOBUTYRIC ACID; RECEPTORS; BIOCHEMICAL REACTION KINETICS; SYMPATHOMIMETICS; AUTORADIOGRAPHY; BRAIN; LIGANDS; RABBITS; SODIUM CHLORIDES; SPECIFICITY; TRITIUM COMPOUNDS; ALKALI METAL COMPOUNDS; AMINO ACIDS; ANIMALS; AUTONOMIC NERVOUS SYSTEM AGENTS; BODY; CARBOXYLIC ACIDS; CENTRAL NERVOUS SYSTEM; CHLORIDES; CHLORINE COMPOUNDS; DRUGS; HALIDES; HALOGEN COMPOUNDS; HYDROGEN COMPOUNDS; KINETICS; MAMMALS; MEMBRANE PROTEINS; NERVOUS SYSTEM; NEUROREGULATORS; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANS; PROTEINS; REACTION KINETICS; SODIUM COMPOUNDS; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Basile, A S, Ostrowski, N L, Gammal, S H, Jones, E A, and Skolnick, P. The GABAA receptor complex in hepatic encephalopathy. Autoradiographic evidence for the presence of elevated levels of a benzodiazepine receptor ligand. United States: N. p., 1990. Web.
Basile, A S, Ostrowski, N L, Gammal, S H, Jones, E A, & Skolnick, P. The GABAA receptor complex in hepatic encephalopathy. Autoradiographic evidence for the presence of elevated levels of a benzodiazepine receptor ligand. United States.
Basile, A S, Ostrowski, N L, Gammal, S H, Jones, E A, and Skolnick, P. 1990. "The GABAA receptor complex in hepatic encephalopathy. Autoradiographic evidence for the presence of elevated levels of a benzodiazepine receptor ligand". United States.
@article{osti_7138041,
title = {The GABAA receptor complex in hepatic encephalopathy. Autoradiographic evidence for the presence of elevated levels of a benzodiazepine receptor ligand},
author = {Basile, A S and Ostrowski, N L and Gammal, S H and Jones, E A and Skolnick, P},
abstractNote = {Autoradiographic analysis was used to examine radioligand binding to benzodiazepine (BZ) and GABAA receptors in the brains of rabbits with hepatic encephalopathy (HE). Thin sections of whole brain from normal rabbits and rabbits with HE were mounted on slides and subdivided into two groups. One group was washed before incubation with radioligand, while the second group was not prewashed. (3H)Flunitrazepam binding to BZ receptors was decreased by 22% to 42% (p less than 0.05) in the cerebral cortex, superior and inferior colliculi, and cerebellum of unwashed sections from rabbits with HE compared to all other groups. The binding of (3H)Ro 15-1788 to unwashed sections from rabbits with HE was reduced by a similar degree (18% to 37%, p less than 0.05) in the cerebral cortex, hippocampus, superior colliculus, and cerebellar cortex. Incubation of sections with the GABA-mimetic muscimol and NaCl produced an additional decrease in (3H)flunitrazepam binding to the cortex and hippocampus (25% to 31%, p less than 0.05) in unwashed HE rabbit brain, but increased radioligand binding (27% to 71%, p less than 0.05) to several regions in control rabbits. No changes in radioligand binding to either GABAA or peripheral benzodiazepine receptors was observed between HE and control rabbit sections. These findings are consistent with previous electrophysiologic and neurochemical observations indicating no significant changes in either the function or density of GABAA or BZ receptors in this model of HE. Further, they indicate that a reversible BZ receptor ligand with agonist properties is present in the brain in HE. This substance may contribute to the enhancement of GABAergic tone observed in this syndrome.},
doi = {},
url = {https://www.osti.gov/biblio/7138041}, journal = {Neuropsychopharmacology; (USA)},
issn = {0893-133X},
number = ,
volume = 3:1,
place = {United States},
year = {Thu Feb 01 00:00:00 EST 1990},
month = {Thu Feb 01 00:00:00 EST 1990}
}