L-Leucine prevents ammonia-induced changes in glutamate receptors in the brain and in visual evoked potentials in the rabbit.
The effect of L-leucine on glutamate receptors in the brain and on visual evoked potentials was studied in hyperammonemic rabbits. Hyperammonemia was induced by the iv infusion of 2.1 mmol NH4Cl/h over 3 hr. Hyperammonemia was followed by a 116% increase in the specific binding of 3H-glutamate to synaptic membranes prepared from the hippocampus. This increase was due to both an increase in the affinity and in the density of the glutamate receptor. The simultaneous infusion of L-leucine (6.7 mmol/hr) completely prevented the ammonia-induced increase in the specific glutamate binding, whereas L-valine and D-leucine had no effect. Hyperammonemia was also associated with typical, reproducible, and reversible changes in visual evoked potentials. The amplitudes of the first negative and the second positive peak decreased, whereas the latencies of these peaks remained unchanged. The simultaneous infusion of L-leucine completely prevented these changes. These findings indicate (1) that L-leucine prevents ammonia-induced changes in the glutamatergic excitatory neurotransmitter system and (2) that pharmacologic doses of L-leucine modulate the effects of hyperammonemia on central neurotransmission as assessed by visual evoked potentials. A causal relationship between the effects of L-leucine on ammonia-induced changes in glutamate receptors and in visual evoked potentials cannot be inferred with confidence. These findings provide a potential alternative explanation for the apparent beneficial effects of infusions of branched-chain amino acids on hepatic encephalography in patients with chronic liver disease.
D000641:Ammonia / Q000097:blood* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D005074:Evoked Potentials, Visual / Q000187:drug effects*; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D007930:Leucine / Q000494:pharmacology*; D011817:Rabbits; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
D005971:Glutamates; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D018698:Glutamic Acid; D000641:Ammonia; D007930:Leucine