Skip to main content
SpringerLink
Log in

The GABA Hypothesis — State of the Art

  • Chapter
Hepatic Encephalopathy, Hyperammonemia, and Ammonia Toxicity

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 368))

Abstract

Before the gamma-aminobutyric acid (GABA) hypothesis was proposed more than a decade ago there had been increasing awareness that the hypotheses of the pathogenesis of hepatic encephalopathy (HE) then in vogue did not adequately account for all of the manifestations of this syndrome. A particular deficiency of those hypotheses was their failure to account for the manifestations of the syndrome in terms of abnormal neural mechanisms (1). Although GABA had been included in lists of substances that had been considered in relation to HE (2), the possibility of an involvement of the GABA neurotransmitter system in its pathogenesis had not been seriously assessed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Schafer, D.F., and Jones, E.A., 1982, Potential neural mechanisms in the pathogenesis of hepatic encephalopathy, in: Progress in Liver Diseases, volume VII, Popper, H. and Schaffner, F. (Eds.), Grune and Stratton, New York, 615–627.

    Google Scholar 

  2. Conn, H.O. and Lieberthal, M.M., 1978, The Hepatic Coma Syndromes and Lactulose, Williams and Wilkins, Baltimore, 1978.

    Google Scholar 

  3. Schafer, D.F., Brody, L.E. and Jones, E.A., 1979, Visual evoked potentials: an objective measurement of hepatic encephalopathy in the rabbit, Gastroenterology 77:A38.

    Google Scholar 

  4. Schafer, D.F., Pappas, S.C., Brody, L.E., Jacobs, R. and Jones EA, 1984, Visual evoked potentials in a rabbit model of hepatic encephalopathy. I. Sequential changes and comparisons with drug-induced comas, Gastroenterology 86:540–545.

    PubMed  CAS  Google Scholar 

  5. Schafer, D.F., Fowler, J.M., Brody, L.E., and Jones, E.A., 1980, Hepatic coma and inhibitory neurotransmission: the enteric bacterial flora as a source of gamma-aminobutyric acid, Gastroenterology 79:1052.

    Google Scholar 

  6. Paul, S.M., Marangos, P.J., and Skolnick, P., 1981, The benzodiazepine-GABA-chloride ionophore receptor complex: common site of minor tranquiliser action, Biol. Psych. 16:213–229.

    CAS  Google Scholar 

  7. Schafer, D.F., and Jones, E.A., 1982, Hepatic encephalopathy and the gamma-aminobutyric-acid neutotransmitter system, Lancet i:18–19.

    Article  Google Scholar 

  8. Smialowski, A., 1978, The effect of intrahippocampal administration of gamma-aminobutyric acid (GABA), in: Amino Acids as Chemical Transmitters, Fonnum, F. (Ed.), Plenum Press, New York, 1977–1980.

    Google Scholar 

  9. Bassett, M.L., Mullen, K.D., Skolnick, P., and Jones, E.A., 1987, Amelioration of hepatic encephalopathy by pharmacological antagonism of the GABAA-benzodiazepine receptor complex in a rabbit model of fulminant hepatic failure, Gastroenterology 93:1069–1077.

    PubMed  CAS  Google Scholar 

  10. Schafer, D.F., Waggoner, J.G., and Jones, E.A., 1980, Sera from rabbits in acute hepatic coma inhibit the binding of [3H] gamma-aminobutyric acid to neural membranes, Gastroenterology 78:1320.

    Google Scholar 

  11. Schafer, D.F., Thakur, A.K., and Jones, E.A., 1980, Acute hepatic coma and inhibitory neurotransmission: increase in gamma-aminobutyric acid levels in plasma and receptors in brain, Gastroenterology 79:1123.

    Google Scholar 

  12. Schafer, D.F., Fowler, J.M., and Jones, E.A., 1981, Colonic bacteria: a source of gamma-aminobutyric acid in blood, Proc. Soc. Exp. Biol. Med. 167:301–303.

    PubMed  CAS  Google Scholar 

  13. Horowitz, M.E., Schafer, D.F., Molnar, P., Jones, E.A., Blasberg, R.G., Patlak, C.S., Waggoner,J., and Fenstermacher, J.D., 1983, Increased blood-brain transfer in a rabbit model of acute liver failure, Gastroenterology 84:1003–1011.

    PubMed  CAS  Google Scholar 

  14. Schafer, D.F., Fowler, J.M., Munson, P.J., Thakur, A.K., Waggoner, J.G., and Jones, E.A., 1983,Gamma-aminobutyric acid and benzodiazepine receptors in an animal model of fulminant hepatic failure, J. Lab. Clin. Med. 102:870–880.

    PubMed  CAS  Google Scholar 

  15. Lefkowitz, R.J., Caron, M.G., Stiles, G.L, 1984, Mechanisms of membrane receptor regulation, N. Engl. J. Med. 310:1570–1579.

    Article  PubMed  CAS  Google Scholar 

  16. Bakti, G., Fisch, H.U., Karlaganis, G., Minder,C., and Bircher, J., 1987, Mechanism of the excessive sedative response of cirrhotics to benzodiazepines: model experiments with triazolam, Hepatology 7:629–638.

    Article  PubMed  CAS  Google Scholar 

  17. Ferenci, P., Schafer, D.F., Kleinberger, G., Hoofnagle, J.H., and Jones, E.A., 1983, Serum levels of gamma-aminobutyric-acid-like activity in acute and chronic hepatocellular disease, Lancet ii:811–814.

    Article  Google Scholar 

  18. van Berlo, C.L.H., de Jonge, H.R., van den Bogaard, A.E.J.M., Janssen, M.A., van Eijk, H.M.H.,van der Heijden, M.A.H., and Soeters, P.B., 1987, Gamma-aminobutyric acid production in small and large intestine of normal and germ-free Wistar rats. Influence of food intake and intestinal flora, Gastroenterology 93:472–479.

    PubMed  Google Scholar 

  19. Ferenci, P., Ebner, J., Zimmermann, C., Kikuta, C., Roth, E., and Hausinger, D., 1988,Overestimation of serum concentrations of gamma-aminobutyric acid in patients with hepatic encephalopathy by the gamma-aminobutyric acid-radioreceptor assay, Hepatology 8:69–72.

    Article  PubMed  CAS  Google Scholar 

  20. Maddison, J.E., Leong, D.K., Dodd, P.R., and Johnson, G.A.R., 1990, Plasma GABA-like activity in rats with hepatic encephalopathy is due to GABA and taurine, Hepatology 11:105–110.

    Article  PubMed  CAS  Google Scholar 

  21. Minuk, G.Y., Winder, A., Burgess, E.D., and Sargeant, E.J., 1985, Serum gamma-aminobutyric acid (GABA) levels in patients with hepatic encephalopathy, Hepatogastroenterology 32:171–174.

    PubMed  CAS  Google Scholar 

  22. Levy, L.J., Leek, J., and Losowsky, M.S., 1987, Evidence for gamma-aminobutyric acid as the inhibitor of gamma-aminobutyric acid binding in the plasma of humans with liver disease and hepatic encephalopathy, Clin. Sci. 73:531–534.

    PubMed  CAS  Google Scholar 

  23. Albrecht, J., and Rafalowska, U., 1987, Enhanced potassium-stimulated gamma-aminobutyric acid release by astrocytes derived from rats with early hepatic encephalopathy, J. Neurochem. 49:9–11.

    Article  PubMed  CAS  Google Scholar 

  24. Jones, E.A., Gammal, S.H., Basile, A.S., Mullen, K.D., Bassett, M.L., Schafer, D.F., and Skolnick,P., 1988, Hepatic encephalopathy and benzodiazepine receptor ligands, in: Hepatic Encephalopathy. Pathophysiology and Treatment, Butterworth, R.F., and Layrargues, G.P. (Eds), Humana Press, Clifton, New Jersey, 273–286.

    Google Scholar 

  25. Oldendorf, W.H., 1971, Brain uptake of radiolabeled amino acids, amines and hexoses after arterial injection, Am. J. Physiol. 221:1629–1639.

    PubMed  CAS  Google Scholar 

  26. Goldstein, G.W., 1984, The role of brain capillaries in the pathogenesis of hepatic encephalopathy,Hepatology 4:565–567.

    Article  PubMed  CAS  Google Scholar 

  27. Lo, W.D., Ennis, S.R., Goldstein, G.W., McNeely, D.L., and Betz, A.L., 1987, The effects of galactosamine-induced hepatic failure upon blood-brain barrier permeability, Hepatology 7:452–456.

    Article  PubMed  CAS  Google Scholar 

  28. Knudsen, G.M., Poulsen, H.E., Paulsen, O.B., 1988, Blood-brain barrier permeability in galactosamine-induced hepatic encephalopathy. No evidence for increased GABA transport, J. Hepatol. 6:187–192.

    Article  PubMed  CAS  Google Scholar 

  29. Mullen, K.D., Schafer, D.F., Cuchi, P., Rossle, M., Maynard, T.F., and Jones, E.A., 1988,Evaluation of the suitability of galactodamine-induced fulminant hepatic failure as a model of hepatic encephalopathy in the rat and the rabbit, in: Advances in Ammonia Metabolism and Hepatic Encephalopathy, Soeters, P.B., Wilson, J.H.P., Meijer, A.J., and Holm, E. (Eds.), Elsevier Science Publishers, Amsterdam, 205–212.

    Google Scholar 

  30. Blitzer, B.L., Waggoner, J.G., Jones, E.A., Gralnick, H., Towne, D., Butler, J., Weise, V., Kopin,I., Walters, I., Teychenne, P.F., Goodmam, D.G., and Berk, P.D., 1978, A model of fulminant hepatic failure in the rabbit, Gastroenterology 74:664–671.

    PubMed  CAS  Google Scholar 

  31. Traber, P.G., Ganger, G.R., and Blei, A.T., 1986, Brain edema in rabbits with galactosamine-induced fulminant hepatitis: regional differences and effects on intracranial pressure, Gastroenterology 91:1347–1356.

    PubMed  CAS  Google Scholar 

  32. Traber, P.G., DelCanto, M.D., Ganger, D.R., and Blei, A.T., 1987, Electronmicroscopic evaluation of brain edema in rabbits with galactosamine-induced fulminant hepatic failure: ultrastructure and integrity of the blood-brain barrier, Hepatology 7:1272–1277.

    Article  PubMed  CAS  Google Scholar 

  33. Bassett, M.L., Mullen, K.D., Scholz, B., Fenstermacher, J.D., and Jones, E.A., 1990, Increased brain uptake of gamma-aminobutyric acid in a rabbit model of hepatic encephalopathy, Gastroenterology 98:747–757.

    PubMed  CAS  Google Scholar 

  34. Cooper, J.R., Bloom, F.E., Roth, R.H., 1991, The Biochemical Basis of Neuropharmacology,Oxford University Press, New York, 1991.

    Google Scholar 

  35. Wysmyk-Cybula, U., Dabrowiecki, Z., and Albrecht, J., 1986, Changes in the metabolism and binding of GABA in the rat brain in thioacetamide-induced hepatogenic encephalopathy, Biomed. Biochim. Acta 45:413–419.

    PubMed  CAS  Google Scholar 

  36. Zimmermann, C, Ferenci, P., Pifl, C., Yurdaydin, C., Ebner, J., Lassman, H., Roth, E., and Hortnagl, H., 1989, Hepatic encephalopathy in thioacetamide-induced acute liver failure: characterization of an improved model and study of amino acid-ergic neurotransmission, Hepatology 9:594–601.

    Article  PubMed  CAS  Google Scholar 

  37. Moroni, F., Riggio, O., Carla, V., Festuccia, V., Ghinelli, F., Marino, I.R., Merli, M., Natali, L.,Pedretti, G., Fiaccadori, F., and Capocaccia, L., 1987, Hepatic encephalopathy: lack of changes of gamma-aminobutyric acid content in plasma and cerebrospinal fluid, Hepatology 7:816–820.

    Article  PubMed  CAS  Google Scholar 

  38. Ungerstedt, U., 1984, Measurement of neurotransmitter release by intracranial dialysis, in:Measurement of Neurotransmitter Release, Marsden, C.A. (Ed.), John Wiley and Sons, New York, 81–105.

    Google Scholar 

  39. Enna, S.J., and Snyder, S.H., 1977, Influence of ions, enzymes, and detergents on gamma-aminobutyric acid receptor binding in synaptic membranes of rat brain, Mol. Pharmacol. 13:442–453.

    PubMed  CAS  Google Scholar 

  40. Baraldi, M., and Zeneroli, M.L., 1982, Experimental hepatic encephalopathy: changes in the binding of gamma-aminobutyric acid, Science 216:427–428.

    Article  PubMed  CAS  Google Scholar 

  41. Schenker, S., and Brady III, C.E., 1988, Pathogenesis of hepatic encephalopathy, in: Hepatic Encephalopathy: Management with Lactulose and Related Carbohydrates, Conn, H.O., and Bircher, J. (Eds.), Medi-Ed Press, East Lansing, Michigan, 15–30.

    Google Scholar 

  42. Jones, E.A., and Skolnick, P., 1990, Benzodiazepine receptor ligands and the syndrome of hepatic encephalopathy, in: Progress in Liver Diseases, volume IX, Popper, H., and Schaffner, F. (Eds.), W.B. Saunders, Philadelphia, 345–370.

    Google Scholar 

  43. Rossle, M., Mullen, K.D., and Jones, E.A., 1989, Cortical benzodiazepine receptor binding in a rabbit model of hepatic encephalopathy: the effect of Triton X-100 on receptor solubilization, Metabolic Brain Dis. 4:203–212.

    Article  CAS  Google Scholar 

  44. Basile, A.S., Gammal, S.H., Jones, E.A., and Skolnick, P., 1989, GABAA receptor complex in an experimental model of hepatic encephalopathy: evidence for elevated levels of an endogenous benzodiazepine receptor ligand, J. Neurochem. 53:1057–1063.

    Article  PubMed  CAS  Google Scholar 

  45. Basile, A.S., Ostrowski, N.L., Gammal, S.H., Jones, E.A., and Skolnick, P., 1990, The GABAA receptor complex in hepatic encephalopathy. Autoradiographic evidence for the presence of elevated levels of a benzodiazepine receptor ligand, Neuropsychopharmacol 3:61–71.

    CAS  Google Scholar 

  46. Pappas, S.C., Ferenci, P., Schafer, D.F., and Jones, E.A., 1984, Visual evoked potentials in a rabbit model of hepatic encephalopathy. II. Comparison of hyperammonemic encephalopathy, postictal coma and coma induced by synergistic neurotoxins, Gastroenterology 86:546–551.

    PubMed  CAS  Google Scholar 

  47. Jones, D.B., Mullen, K.D., Roessle, M., Maynard, T., and Jones, E.A., 1987, Hepatic encephalopathy: application of visual evoked responses to test hypotheses of its pathogenesis in rats, J. Hepatol. 4:118–126.

    Article  PubMed  CAS  Google Scholar 

  48. Ferreira, M.R., Gammal, S.H., and Jones, E.A., 1988, Hepatic encephalopathy: evidence of increased GABA-mediated neurotransmission in a rat model of fulminant hepatic failure, Gastroenterology 94:A616.

    Google Scholar 

  49. Jones, E.A., Basile, A.S., Mullen, K.D., and Gammal, S.H., 1990, Flumazenil: potential implications for hepatic encephalopathy, Pharmac. Ther. 45:331–343.

    Article  CAS  Google Scholar 

  50. Basile, A.S., Gammal, S.H., Mullen, K.D., Jones, E.A., and Skolnick, P., 1988, Differential responsiveness of cerebellar Purkinje neurons to GABA and benzodiazepine receptor ligands in an animal model of hepatic encephalopathy, J. Neurosci. 8:2414–2421.

    PubMed  CAS  Google Scholar 

  51. Gammal, S.H., Basile, A.S., Geller, D., Skolnick, P., and Jones, E.A., 1990, Reversal of the behavioral and electrophysiological abnormalities of an animal model of hepatic encephalopathy by benzodiazepine receptor ligands, Hepatology 11:371–378.

    Article  PubMed  CAS  Google Scholar 

  52. Bosman, D.K., van der Buijs, C.A.C.G., de Haan, J.G., Maas, M.A.W., and Chamuleau, R.A.F.M.,1991, The effects of benzodiazepine receptor antagonists and partial inverse agonists in acute hepatic encephalopathy in the rat, Gastroenterology 101:772–781.

    PubMed  CAS  Google Scholar 

  53. Steindl, P., Puspok, A., Druml, W., and Ferenci, P., 1991, Beneficial effect of pharmacological modulation of the GABAA-benzodiazepine receptor on hepatic encephalopathy in the rat: comparison with uremic encephalopathy, Hepatology 14:963–968.

    Article  PubMed  CAS  Google Scholar 

  54. Haefely, W., Kyburz, E., Gerecke, M., and Monier, M., 1985, Recent advances in the molecular pharmacology of benzodiazepine receptors and in the structure-activity relationships of their agonists and antagonists, Adv. Drug. Res. 14:165–322.

    CAS  Google Scholar 

  55. Gardner, C.R., 1988, Pharmacological profiles in vivo of benzodiazepine receptor ligands, Drug.Devel. Res. 12:1–28, 1988.

    Article  CAS  Google Scholar 

  56. Jones, E.A., 1991, Benzodiazepine receptor ligands and hepatic encephalopathy: Further unfolding of the GABA story, Hepatology 14:1286–1290.

    Article  PubMed  CAS  Google Scholar 

  57. Grimm, G., Ferenci, P., Katzenschlager, R., Madl, C., Schneeweiss, B., Laggner, A.N., Lenz, K.,and Gangl, A., 1988, Improvement in hepatic encephalopathy treated with flumazenil, Lancet ii:1392–1394.

    Article  Google Scholar 

  58. Bansky, G., Meier, P.J., Riederer, E., Walser, H., Ziegler, W.H., and Schmid, M., 1989, Effects of the benzodiazepine receptor antagonist flumazenil in hepatic encephalopathy in humans, Gastroenterology 97:744–750.

    PubMed  CAS  Google Scholar 

  59. Basile, A.S., Jones, E.A., and Skolnick, P., 1991, The pathogenesis and treatment of hepatic encephalopathy: evidence for the involvement of benzodiazepine receptor ligands, Pharm. Rev. 43:27–71.

    PubMed  CAS  Google Scholar 

  60. Ferenci, P., Grimm, G., Meryn, S., and Gangl, A., 1989, Successful long-term treatment of portal-systemic encephalopathy by the benzodiazepine antagonist flumazenil, Gastroenterology 96:240–243.

    PubMed  CAS  Google Scholar 

  61. Baker, B.L., Morrow, A.L., Vergalla, J., Paul, S.M., and Jones, E.A., 1990, Gamma-aminobutyric acid (GABAA) receptor-function in a rat model of hepatic encephalopathy, Metabolic Brain Dis. 5:1285–1293.

    Google Scholar 

  62. Rossle, M., Deckert, J., and Jones, E.A., 1989, Autoradiographic analysis of GABA-benzodiazepine receptors in an animal model of acute hepatic encephalopathy, Hepatology 10:143–147.

    Article  PubMed  CAS  Google Scholar 

  63. Basile, A.S., 1991, The contribution of endogenous benzodiazepine receptor ligands to the pathogenesis of hepatic encephalopathy, Synapse 7:141–150.

    Article  PubMed  CAS  Google Scholar 

  64. Albrecht, J., Hilgier, W., and Rafalowska, U., 1990, Activation of arginine metabolism to glutamate in rat brain synaptosomes in thioacetamide-induced hepatic encephalopathy: an adaptive response? J. Neuroscience Res. 25:125–130.

    Article  CAS  Google Scholar 

  65. Wysmyk, U., Oja, S.S., Saransaari, P., and Albrecht, J., 1992, Enhanced GABA release in cerebral cortical slices from rats with thioacetamide-induced hepatic encephalopathy, Neurochem. Res. 17:1187–1190.

    Article  PubMed  CAS  Google Scholar 

  66. Oja, S.S., Saransaari, P., Wysmyk, U., and Albrecht, J., 1993, Loss of GABAB binding sites in the cerebral cortex of rats with acute hepatic encephalopathy, Brain Res. 629:355–357.

    Article  PubMed  CAS  Google Scholar 

  67. Anderson, B., 1984, A proposed theory for the encephalopathies of Reye’s syndrome and hepatic encephalopathy, Med. Hypotheses 15:415–420.

    Article  PubMed  CAS  Google Scholar 

  68. Bansky, G., Meier, P.J., Ziegler, W.H., Walser, H., Schmid, M., and Huber, M., 1985, Reversal of hepatic coma by benzodiazepine antagonist (Ro 15–1788), Lancet i:1324–1325.

    Google Scholar 

  69. Baraldi, M., Zeneroli, M.L., Ventura, E., Penne, A., Pinelli, G., Ricci, P., and Santi, M., 1984,Supersensitivity of benzodiazepine receptors in hepatic encephalopathy due to fulminant hepatic failure in the rat: reversal by a benzodiazepine antagonist, Clin. Sci. 67:167–175.

    PubMed  CAS  Google Scholar 

  70. Bassett, M.L., Mullen, K.D., Skolnick, P., and Jones, E.A., 1985, GABA and benzodiazepine receptor antagonists ameliorate hepatic encephalopathy in a rabbit model of fulminant hepatic failure, Hepatology 5:1032.

    Google Scholar 

  71. Scollo-Lavizzari, G., and Steinmann, E., 1985, Reversal of hepatic coma by benzodiazepine antagonist (Ro 15–1788), Lancet i:1324.

    Article  Google Scholar 

  72. van der Rijt, C.C.D., de Knegt, R.J., Schalm, S.W., Terpstra, O.T., and Mechelse, K., 1990,Flumazenil does not improve hepatic encephalopathy associated with acute ischemic liver failure in the rabbit. Metabolic Brain Dis. 5:131–141, 1990.

    Article  Google Scholar 

  73. Mullen, K.D., Martin, J.V., Mendelson, W.B., Kaminsky-Russ, K., and Jones, E.A., 1989,Evidence for the presence of a benzodiazepine receptor binding substance in cerebrospinal fluid of a rabbit model of hepatic encephalopathy, Metabolic Brain Dis. 4:253–260.

    Article  CAS  Google Scholar 

  74. Olasmaa, M., Rothstein, J.D., Guidotti, A., Weber, R.J., Paul, S.M., Spector, S., Zeneroli, M.L.,Baraldi, M., and Costa, E., 1990, Endogenous benzodiazepine receptor ligands in human and animal hepatic encephalopathy, J. Neurochem. 55:2015–2023.

    Article  PubMed  CAS  Google Scholar 

  75. Basile, A.S., Pannell, L., Jaouni, T., Gammal, S.H., Fales, H.M., Jones, E.A., and Skolnick, P.,1990, Brain concentrations of benzodiazepines are elevated in an animal model of hepatic encephalopathy, Proc Natl Acad Sci (USA) 87:5263–5267.

    Article  CAS  Google Scholar 

  76. Mullen, K.D., Szauter, K.M., and Kaminsky-Russ, K., 1990, “Endogenous” benzodiazepine activity in body fluids of patients with hepatic encephalopathy, Lancet 336:81–83.

    Article  PubMed  CAS  Google Scholar 

  77. Basile, A.S., Hughes, R.D., Harrison, P.M., Murata, Y., Pannell, L., Jones, E.A., Williams, R., and Skolnick, P., 1991, Elevated brain concentrations of 1,4-benzodiazepines in fulminant hepatic failure, N. Engl. J. Med. 325:473–478.

    Article  PubMed  CAS  Google Scholar 

  78. Yurdaydin, C., Gu, Z-Q., Nowak, G., Fromm, C., Holt, A.G., and Basile, A.S., 1993,Benzodiazepine receptor ligands are elevated in an animal model of hepatic encephalopathy: relationship between brain concentration and severity of encephalopathy, J. Pharm. Exp. Ther. 265:565–571.

    CAS  Google Scholar 

  79. Basile, A.S., Hughes, R.D., Harrison, P.M., Gu, Z-Q., Pannell, L., McKinnon, A., Jones, E.A., and Williams, R., 1994, Correlation between plasma benzodiazepine receptor ligand concentrations and the severity of hepatic encephalopathy in patients with fulminant hepatic failure, Hepatology 19:112–121.

    Article  PubMed  CAS  Google Scholar 

  80. Mullen, K.D., Martin, J.V., Mendelson, W.B., Bassett, M.L., and Jones, E.A., 1988, Could an endogenous benzodiazepine ligand contribute to hepatic encephalopathy? Lancet i:457–459.

    Article  Google Scholar 

  81. Jones, E.A., Skolnick, P., Gammal, S.H., Basile, A.S., and Mullen, K.D., 1989, The gamma-aminobutyric acid A (GABAA) receptor complex and hepatic encephalopathy. Some recent advances, Ann. Intern. Med. 110:532–546.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Health, London, UK

    E. Anthony Jones

  2. Department of Gastroenterology, University of Ankara, Ankara, Turkey

    Cihan Yurdaydin

  3. Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, Maryland, USA

    Anthony S. Basile

Authors
  1. E. Anthony Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cihan Yurdaydin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anthony S. Basile
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Instituto de Investigaciones Citologicas de la F. I. B., Valencia, Spain

    Vicente Felipo  & Santiago Grisolia  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Springer Science+Business Media New York

About this chapter

Cite this chapter

Jones, E.A., Yurdaydin, C., Basile, A.S. (1994). The GABA Hypothesis — State of the Art. In: Felipo, V., Grisolia, S. (eds) Hepatic Encephalopathy, Hyperammonemia, and Ammonia Toxicity. Advances in Experimental Medicine and Biology, vol 368. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1989-8_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-1989-8_9

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5820-6

  • Online ISBN: 978-1-4615-1989-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation