Affinities and densities of high-affinity [3H]muscimol (GABA-A) binding sites and of central benzodiazepine receptors are unchanged in autopsied brain tissue from cirrhotic patients with hepatic encephalopathy.
The integrity of GABA-A receptors and of central benzodiazepine receptors was evaluated in membrane preparations from prefrontal cortex and caudate nuclei obtained at autopsy from nine cirrhotic patients who died in hepatic coma and an equal number of age-matched control subjects. Histopathological studies revealed Alzheimer Type II astrocytosis in all cases in the cirrhotic group; controls were free from neurological, psychiatric or hepatic diseases. Binding to GABA-A receptors was studied using [3H]muscimol as radioligand. The integrity of central benzodiazepine receptors was evaluated using [3H]flunitrazepam and [3H]Ro15-1788. Data from saturation binding assays was analyzed by Scatchard plot. No modifications of either affinities (Kd) or densities (Bmax) of [3H]muscimol of central benzodiazepine binding sites were observed. These findings do not support recent suggestions that alterations of either high-affinity GABA or benzodiazepine receptors play a significant role in the pathogenesis of hepatic encephalopathy.
Butterworth
R F
RF
Laboratory of Neurochemistry, André-Viallet Clinical Research Center, Hôpital Saint-Luc, University of Montreal, Quebec, Canada.
Lavoie
J
J
Giguère
J F
JF
Pomier-Layrargues
G
G
D000345:Affinity Labels / Q000494:pharmacology; D000368:Aged; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001923:Brain Chemistry; D005442:Flumazenil / Q000494:pharmacology; D005445:Flunitrazepam / Q000494:pharmacology; D006501:Hepatic Encephalopathy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009118:Muscimol / Q000378:metabolism*; D011869:Radioligand Assay; D011963:Receptors, GABA-A / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D014316:Tritium
D000345:Affinity Labels; D011963:Receptors, GABA-A; D014316:Tritium; D009118:Muscimol; D005442:Flumazenil; D005445:Flunitrazepam