Increased densities of peripheral-type benzodiazepine receptors in brain autopsy samples from cirrhotic patients with hepatic encephalopathy

✍ Scribed by Joel Lavoie; Gilles Pomier Layrargues; Dr. Roger F. Butterworth

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 544 KB
• Volume: 11
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840110524

✦ Synopsis

Peripheral-type benzodiazepine receptors were evaluated using the specific ligand ['HI-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 I1 astrocytosis in the brains of all cirrhotic patients. Saturation-binding assays revealed a single saturable binding site for ['HI-PK 11196 in brain, with affinities in the 2-to 3-nmol/L range. Diazepam was found to be a relatively potent inhibitor of 'H-PK 11195 binding (ICso = 253 nmoliL), whereas the central benzodiazepine antagonist Ro 15-1788 displaced 'H-PK 11195 binding with low affinity (ICso > 40 pmol/L). Densities of PHI-PK 11195 binding sites were found to be increased by 48% (p < 0.01) and 25% (p < 0.05) in frontal cortex and caudate nuclei, respectively, from cirrhotic patients. Densities of ['HI-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. (HEPATOLOGY 1990;11:874-878.) Increasing interest is being focused on the role of benzodiazepine receptors in the pathogenesis of hepatic encephalopathy (HE) in patients with acute or chronic liver disease. The catalysts for these studies were initial observations of increased benzodiazepine binding sites in brains of animals with experimental HE (1, 2) and