PMID- 1965008
OWN - NLM
STAT- MEDLINE
DCOM- 19910517
LR  - 20191028
IS  - 0885-7490 (Print)
IS  - 0885-7490 (Linking)
VI  - 5
IP  - 4
DP  - 1990 Dec
TI  - Gamma-aminobutyric acid (GABAA) receptor-function in a rat model of hepatic 
      encephalopathy.
PG  - 185-93
AB  - The functional activity of the gamma-aminobutyric acid (GABAA) receptor-chloride 
      ionophore complex was studied in rats with hepatic encephalopathy (HE) secondary 
      to thioacetamide-induced fulminant hepatic failure (FHF). Muscimol stimulation 
      and benzodiazepine potentiation of GABA receptor-mediated 36Cl- uptake into 
      cerebral cortical synaptoneurosomes was compared in HE and control rats. 
      [3H]Flumazenil binding assays were conducted to determine whether the levels of 
      endogenous benzodiazepine-like ligands in extracts of cortex were increased with 
      stages of encephalopathy in this animal model of HE. In both control and HE rats 
      maximal uptake of 36Cl- via the GABAA receptor complex occurred at muscimol 
      concentrations of 30 microM. Potentiation of muscimol-stimulated 36Cl- uptake 
      into synaptoneurosomes by diazepam (5 microM) was equivalent in both groups. 
      Aqueous extracts of proteolytically digested homogenates of cerebral cortices 
      prepared from control and HE rats were effective in stimulating 36Cl- uptake into 
      synaptoneurosomes. Alkaline organic extracts of proteolytically digested 
      homogenates of cerebral cortices from HE rats were more effective than 
      corresponding extracts from controls at inhibiting the binding of [3H]flumazenil. 
      Inhibition of [3H] fumazenil binding by organic extracts derived from the 
      cerebral cortices of HE rats did not increase with progression of encephalopathy. 
      The results show that muscimol-stimulated 36Cl- uptake into synaptoneurosomes 
      and, consequently, GABAA receptor-mediated chloride channel function are not 
      significantly altered in the model of HE studied and are consistent with the 
      hypothesis that HE results in an increased availability of one or more endogenous 
      ligands which can augment GABA receptor-gated chloride conductance.
FAU - Baker, B L
AU  - Baker BL
AD  - Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney 
      Diseases, National Institutes of Health, Bethesda, Maryland 20892.
FAU - Morrow, A L
AU  - Morrow AL
FAU - Vergalla, J
AU  - Vergalla J
FAU - Paul, S M
AU  - Paul SM
FAU - Jones, E A
AU  - Jones EA
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Metab Brain Dis
JT  - Metabolic brain disease
JID - 8610370
RN  - 0 (Chlorides)
RN  - 0 (Receptors, GABA-A)
RN  - 40P7XK9392 (Flumazenil)
SB  - IM
MH  - Animals
MH  - Cerebral Cortex/metabolism
MH  - Chlorides/metabolism
MH  - Disease Models, Animal
MH  - Flumazenil/metabolism
MH  - Hepatic Encephalopathy/*metabolism
MH  - Radioligand Assay
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Receptors, GABA-A/*metabolism
MH  - Statistics as Topic
MH  - Synaptosomes/metabolism
EDAT- 1990/12/01 00:00
MHDA- 1990/12/01 00:01
CRDT- 1990/12/01 00:00
PHST- 1990/12/01 00:00 [pubmed]
PHST- 1990/12/01 00:01 [medline]
PHST- 1990/12/01 00:00 [entrez]
AID - 10.1007/BF00997072 [doi]
PST - ppublish
SO  - Metab Brain Dis. 1990 Dec;5(4):185-93. doi: 10.1007/BF00997072.