Direct Enhancement of Gaba-Ergic Neurotransmission by Ammonia

摘要: Ammonia (NH4 +) has been implicated since the 1950’s as primary pathogenic agent contributing to encephalopathies associated with hepatic failure1. NH4 + is clearly neurotoxic, but molecular mechanisms by which ammonia exerts its toxic actions remain subject of active investigation. Because neurologic manifestations these are consistent central nervous system depression, increased activity neuronal pathways using principle inhibitory neurotransmitter, γ-aminobutyric acid (GABA) appeared likely contribute pathogenesis syndromes. Despite ample evidence for presence both GABAergic neurotransmission and elevated concentrations in brain during failure, two appear be mutually exclusive. However, recent investigations suggest that linked, may enhance directly interacting GABAA receptor at pathophysiologically relevant concentrations. These new findings not only have important implications failure congenital hyperammonemia syndromes, provide a locus development treatment modalities.