Hepatic encephalopathy and the gamma-aminobutyric-acid neurotransmitter system

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.