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Hepatocytes explanted in the spleen preferentially express carbamoylphosphate synthetase rather than glutamine synthetase

Authors

  • Wouter H. Lamers M.D., Ph.D.,

    Corresponding author
    1. Department of Anatomy and Embryology, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands
    • Department of Anatomy and Embryology, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands
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  • Willem Been,

    1. Department of Anatomy and Embryology, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands
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  • Robert Charles,

    1. Department of Anatomy and Embryology, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands
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  • Antoon F. M. Moorman

    1. Department of Anatomy and Embryology, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands
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Abstract

Urea cycle enzymes and glutamine synthetase are essential for NH3 detoxification and systemic pH homeostasis in mammals. Carbamoylphosphate synthetase, the first and flux-determining enzyme of the cycle, is found only in a large periportal compartment, and glutamine synthetase is found only in a small, complementary pericentral compartment. Because it is not possible to manipulate experimentally the intrahepatic distribution of carbamoylphosphate synthetase and glutamine synthetase, we looked for conditions in which explanted hepatocytes would exhibit either the carbamoylphosphate synthetase phenotype or glutamine synthetase phenotype. In the spleen hepatocytes either settle as individual cells or in small agglomerates. The dispersed cells only express the carbamoylphosphate synthetase phenotype. Within the agglomerates, sinusoids that drain on venules develop. Hepatocytes surrounding the venules stain only weakly for carbamoylphosphate synthetase but are strongly positive for glutamine synthetase. These observations were made for explanted embryonic hepatocytes (no prior expression of either carbamoylphosphate synthetase or glutamine synthetase), neonatal hepatocytes (compartments of gene expression not yet established) and adult periportal and pericentral hepatocytes. (HEPATOLOGY 1990;12:701–709).

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