[Ammonia and GABA-ergic neurotransmission in pathogenesis of hepatic encephalopathy].
Pathogenesis of hepatic encephalopathy has not been fully revealed and there are many factors which may affect its development. Ammonia and changes in GABA-ergic neurotransmission seem to be the most essential of these factors. Hepatic encephalopathy is frequently, though not always, accompanied by elevated blood ammonia level. Due to the changes in permeability of blood-brain barrier the ammonia level in the brain also increases which results in both stimulating and inhibitory neurotransmission disturbances. Ammonia also affects abnormal interaction of metabolic neurones and astrocytes as well as glutamine-serotonin balance. Another essential factor affecting hepatic encephalopathy development are disturbances in GABA-ergic neurotransmission connected with GABAA receptor complex. When the liver is damaged GABA-ergic neurotransmission increases due to a higher GABA level, natural benzodiazepine receptor agonists as well as neurosteroids synthesised in astrocytes. Many studies point to the fact that ammonia and GABA-ergic neurotransmission disturbances interrelate with each other. There is a concept saying that both these factors cause hepatic encephalopathy. Ammonia may indirectly increase GABA-ergic neurotransmission and also inhibit the function of the central nervous system by synergistic activity with benzodiazepine receptor ligands. So far it is not known whether GABA-ergic neurotransmission is affected by ammonia only or by other factors as well.
Helewski
Krzysztof
K
I Katedry i Zakładu Histologii i Embriologii w Zabrzu Slaskiej Akademii Medycznej w Katowicach.
Kowalczyk-Ziomek
Grazyna
G
Konecki
Janusz
J
D000641:Ammonia / Q000378:metabolism*; D006501:Hepatic Encephalopathy / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018377:Neurotransmitter Agents; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D000641:Ammonia