Increased densities of peripheral-type benzodiazepine receptors in brain autopsy samples from cirrhotic patients with hepatic encephalopathy.
Peripheral-type benzodiazepine receptors were evaluated using the specific ligand [3H]-PK 11195 in brain homogenates from nine cirrhotic patients who died in hepatic coma and from an equal number of age-matched control subjects. Histopathological studies showed evidence of severe Alzheimer type II astrocytosis in the brains of all cirrhotic patients. Saturation-binding assays revealed a single saturable binding site for [3H]-PK 11195 in brain, with affinities in the 2- to 3-nmol/L range. Diazepam was found to be a relatively potent inhibitor of 3H-PK 11195 binding (IC50 = 253 nmol/L), whereas the central benzodiazepine antagonist Ro 15-1788 displaced 3H-PK 11195 binding with low affinity (IC50 greater than 40 mumols/L). Densities of [3H]-PK 11195 binding sites were found to be increased by 48% (p less than 0.01) and 25% (p less than 0.05) in frontal cortex and caudate nuclei, respectively, from cirrhotic patients. Densities of [3H]-PK 11195 binding sites in frontal cortex from two nonencephalopathic cirrhotic patients were not significantly different from control values. No concomitant changes of affinities of these binding sites were observed. Because it has been suggested that peripheral-type benzodiazepine receptors may be localized on mitochondrial membranes and may therefore be involved in cerebral oxidative metabolism, the alterations observed in this study could be of pathophysiological significance in hepatic encephalopathy.
Lavoie
J
J
Laboratory of Neurochemistry, André-Viallet Clinical Research Center, Hôpital St.-Luc, University of Montreal, Quebec, Canada.
Layrargues
G P
GP
Butterworth
R F
RF
D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D005355:Fibrosis / Q000150:complications*; D006501:Hepatic Encephalopathy / Q000150:complications*; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D012016:Reference Values
D007546:Isoquinolines; D011963:Receptors, GABA-A; C037850:PK 11195