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Identification of an Acceptor System for γ-Aminobutyric Acid on Isolated Rat Hepatocytes

Authors

  • Gerald Y. Minuk,

    Corresponding author
    1. Liver Diseases Section, Digestive Diseases Branch, National Institute of Arthritis, Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20205
    Current affiliation:
    1. Department of Medicine, Health Sciences Centre, The University of Calgary, Calgary, Alberta, Canada T2N 1N4.
    • Gerald Y. Minuk, M.D., Department of Medicine, Health Sciences Centre, The University of Calgary, Calgary, Alberta, Canada T2N 1N4.
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  • John Vergalla,

    1. Liver Diseases Section, Digestive Diseases Branch, National Institute of Arthritis, Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20205
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  • Peter Ferenci,

    1. Liver Diseases Section, Digestive Diseases Branch, National Institute of Arthritis, Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20205
    Current affiliation:
    1. I. Universitatsklinik fur Gastroenterologie und Hepatologie, Lazarettgasse 14, A-1090 Vienna, Austria.
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  • E. Anthony Jones

    1. Liver Diseases Section, Digestive Diseases Branch, National Institute of Arthritis, Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20205
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  • The results of this study were presented in part at the annual meeting of the American Association for the Study of Liver Diseases, Chicago, November, 1982, and were published in abstract form (He-patology 1982; 2:726).

Abstract

γ-Aminobutyric acid (GABA) is a potent inhibitory neurotransmitter which is synthesized by the enteric bacterial flora and delivered into portal venous blood. To determine whether the liver is likely to play an important role in regulating serum GABA levels, the uptake and metabolism of [3H]GABA by three populations of cells isolated from rat liver were studied. GABA was specifically taken up by hepatocytes but not by endothelial or Kupffer cells. Uptake by hepatocytes was saturable, as well as time and sodium dependent. At 0.5°C, a temperature at which binding of GABA to the cell surface is considered to be the predominant component of the uptake process, the apparent affinity constant (Km) was 0.82 μM and a minimum value for binding velocity (Vmax) was 0.13 μM per min per 5 ± 105 cells. Uptake of [3H]GABA by hepatocytes was markedly inhibited by excess unlabeled GABA (95%), a-aminoisobutyric acid (66%) and bicuculline (58%), but was inhibited much less by alanine (16%) and leucine (29%). These findings suggest that GABA binds specifically to the high affinity acceptor of the A amino acid transport system of rat hepatocytes. Impaired function of this transport system in liver failure could contribute to increased circulating levels of GABA.

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