What is the role of the GABA receptor complex in the pathogenesis of hepatic encephalopathy (HE)?

Updated: Apr 04, 2019
  • Author: David C Wolf, MD, FACP, FACG, AGAF, FAASLD; Chief Editor: BS Anand, MD  more...
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Answer

Answer

GABA is a neuroinhibitory substance produced in the gastrointestinal tract. Of all brain nerve endings, 24%-45% may be GABAergic. For over 20 years, it was postulated that hepatic encephalopathy was the result of increased GABAergic tone in the brain. [18] However, experimental work is changing perceptions regarding the activity of the GABA receptor complex in cirrhosis. [15, 19]

The GABA receptor complex contains binding sites for GABA, benzodiazepines, and barbiturates. It was believed that there were increased levels of GABA and endogenous benzodiazepines in plasma. These chemicals would then cross an extrapermeable blood-brain barrier. Binding of GABA and benzodiazepines to a supersensitive neuronal GABA receptor complex permitted the influx of chloride ions into the postsynaptic neurons, leading to the generation of an inhibitory postsynaptic potential.

However, experimental work has demonstrated that there is no change in the brain GABA or benzodiazepine levels. Similarly, there is no change in the sensitivity of the receptors of the GABA receptor complex. [19]


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