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
✍ Scribed by Roger F. Butterworth; Joël Lavoie; Jean-François Giguère; Gilles Pomier-Layrargues
- Publisher
- John Wiley and Sons
- Year
- 1988
- Tongue
- English
- Weight
- 598 KB
- Volume
- 8
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
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 agematched control subjects. Histopathological studies revealed Alzheimer Type I1 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 ['H]
Rol5-1788. Data from saturation binding assays was analyzed by Scatchard plot. No modifications of either affinities (K,) 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 .
If adequately controlled, measurements of amino acid neurotransmitters, their associated enzymes and receptors in samples of autopsied human brain tissue may provide useful information concerning the pathophysiology of neurological diseases. For example, alterations of cerebral GABA levels and of benzodiazepine (Bz) receptors have been reported in autopsied material in Huntington's disease (1,2) and abnormalities of glutamic acid have been reported in Huntington's disease (3) and in Friedreich's ataxia (4). Using a similar approach, we now report findings on the integrity of GABA and Bz receptors in the brain of cirrhotic patients who died in hepatic coma. The rationale for this approach was based on recent reports of selective alterations of both GABA and Bz receptor binding parameters in experimental