title: Hepatic encephalopathy and the gamma-aminobutyric-acid neurotransmitter system.
abstract: gamma-Aminobutyric acid (GABA), the principal inhibitory neurotransmitter of the mammalian brain, is synthesised by gut bacteria. In a rabbit model the development of hepatic encephalopathy was associated with increased levels of GABA in plasma, increased permeability of the blood-brain barrier, increased numbers of binding-sites for GABA and benzodiazepines in the brain, and a pattern of neural activity similar to that induced by drugs which activate the GABA neurotransmitter system. It is postulated that in liver failure gut-derived GABA passes through a permeable blood-brain barrier and induces its own receptors in the brain, that gut-derived GABA contributes to the neural inhibition of hepatic encephalopathy, and that an increased number of drug-binding sites mediates enhanced sensitivity to barbiturates and benzodiazepines in liver failure.
mesh_terms: D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000818:Animals; D001463:Barbiturates / Q000378:metabolism; D001569:Benzodiazepines / Q000378:metabolism; D001812:Blood-Brain Barrier; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000209:etiology*; D006801:Humans; D007422:Intestines / Q000382:microbiology; D008099:Liver / Q000201:enzymology; D009433:Neural Inhibition; D011817:Rabbits; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D001463:Barbiturates; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase