The contribution of endogenous benzodiazepine receptor ligands to the pathogenesis of hepatic encephalopathy

Journal Article · Fri Feb 01 04:00:00 EST 1991 · Synapse (New York); (USA)

DOI:https://doi.org/10.1002/syn.890070208· OSTI ID:5682023

Basile, A S ^[1]

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1. National Institutes of Health, Betheda, MD (USA)

The involvement of the gamma-aminobutyric acid A(GABAA) receptor complex in the pathogenesis of hepatic encephalopathy (HE) was examined in galactosamine-treated rabbits with HE caused by fulminant hepatic failure. Radioligand binding to the constituent components of the GABAA receptor complex was unchanged in rabbits with HE. However, partially purified extracts from encephalopathic rabbit brain were approximately three times more potent in inhibiting ({sup 3}H)Ro 15-1788 binding to benzodiazepine (BZ) receptors than extracts from control rabbits. The inhibition of radioligand binding to the BZ receptor produced by these extracts was competitive and reversible and was significantly enhanced by GABA. Further purification of these extracts by high-performance liquid chromatography (HPLC) indicated that the inhibitory activity was localized in several peaks, some of which had retention times corresponding to 1,4-benzodiazepine standards. The presence of diazepam in these extracts was confirmed using mass spectroscopy. Both mass spectroscopic and radiometric techniques demonstrated that the concentration of diazepam in brain extracts from encephalopathic rabbits was approximately 4 times greater than control extracts. These findings link the presence of BZ receptor agonists to the development of a neuropathological condition, thereby providing a rational basis for the use of BZ receptor antagonists in the management of HE in man.

• OSTI ID: 5682023
• Journal Information: Synapse (New York); (USA), Journal Name: Synapse (New York); (USA) Vol. 7:2; ISSN 0887-4476; ISSN SYNAE
• Country of Publication: United States
• Language: English

Related Subjects

550901* -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
AMINOBUTYRIC ACID
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL FUNCTIONS
BODY
BRAIN
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CHROMATOGRAPHY
DIGESTIVE SYSTEM DISEASES
DISEASES
DRUGS
FUNCTIONS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LIGANDS
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MASS SPECTROSCOPY
MEMBRANE PROTEINS
NERVES
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PROTEINS
RABBITS
REACTION KINETICS
RECEPTORS
SEPARATION PROCESSES
SPECTROSCOPY
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES