[14C]-L-Valine Binding to Post Mortem Frontal Cortex Homogenates in Hepatic Encephalopathy
In hepatic encephalopathy (HE) the plasma aromatic amino acid (AAA) concentrations are increased, while branched chain amino acid (BCAA) levels are reduced. Increased availability of AAA in particular of tryptophan (TRP) at brain uptake sites will influence brain synthesis and turnover of neurotransmitters like serotonin (5-hydroxytryptamine; 5-HT). In HE increased TRP, 5-HT and 5-hydroxyindole acetic acid (5-HIAA) concentrations and enhanced 5-HT turnover have been demonstrated in human post mortem brain studies with kynurenine synthesis being more pronounced in plasma than in the brain.1 Treatment with BCAA and in particular L-valine (VAL) frequently lead to awakening of patients from hepatic coma2,3 and this effect has been suggested to correlate with normalization of 5-HT disturbances in the brain.1 Corresponding changes in 5-HT receptor activity occur in HE and may be influenced by the administration of VAL. Using radioreceptor ligand binding techniques with 3H-5-HT and 3H-spiro-peridol (R 50–656 as unlabeled ligand to define unspecific binding) it has been shown in human post mortem frontal cortex that 5-HT-1 receptors (labeled by 3H-5-HT) lose binding density with a slight increase in affinity (total specific binding; B: − 58%, KD=−35%) while treatment with VAL normalizes both 5-ET-lmreceptor density (Bmax: −4%) and affinity (KD = 0%) ex vivo. 4These results have been confirmed by in vitro studies using either control tissue or tissue (frontal cortex) from patients dying from severe hepatic failure.
KeywordsFrontal Cortex Hepatic Encephalopathy Aromatic Amino Acid Branch Chain Amino Acid Receptor Density
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