Hepatic Encephalopathy and Benzodiazepine Receptor Ligands

  • E. Anthony Jones
  • Sergio H. Gammal
  • Anthony S. Basile
  • Kevin D. Mullen
  • Mark L. Bassett
  • Daniel F. Schafer
  • Phil Skolnick
Part of the Experimental Biology and Medicine book series (EBAM, volume 22)


Benzodiazepine (BZ) receptor ligands interact with specific binding sites on the GABAA receptor/chloride channel complex on neurons in the central nervous system (CNS) (1) (Figure 1). Such ligands could contribute to or ameliorate hepatic encephalopathy (HE) if the supra-molecular complex itself is involved in this syndrome. The complex includes distinct receptors for BZ ligands and GABA, and a chloride ionophore on which there are binding sites for barbiturates and cage convulsants, such as Picrotoxin. Activation of the effector component of this complex, the chloride channel, is mediated by the binding of GABA to its receptor and is potentiated by the binding of a BZ agonist or a barbiturate to discrete loci on the complex. Activation induces conformational changes in the complex which result in opening of the chloride channel and hyperpolarization of the neuron (1) (Figure 1). This GABA-gated chloride ion conductance is the basis of GABA-mediated inhibitory neurotransmission or “GABAergic tone.”


Hepatic Encephalopathy Fulminant Hepatic Failure Ammonia Metabolism Visual Evoke Response GABAergic Tone 
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Copyright information

© The Humana Press Inc. 1989

Authors and Affiliations

  • E. Anthony Jones
    • 1
  • Sergio H. Gammal
    • 1
  • Anthony S. Basile
    • 1
  • Kevin D. Mullen
    • 1
  • Mark L. Bassett
    • 1
  • Daniel F. Schafer
    • 1
  • Phil Skolnick
    • 1
  1. 1.Liver Diseases Section and Laboratory of Neuroscience, NIDDKNational Institutes of HealthBethesdaUSA

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