| Control of hepatic nitrogen metabolism and glutathione release by cell volume regulatory mechanisms. | |
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MedLine Citation:
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PMID: 2249700 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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1. Urea synthesis was studied in isolated perfused rat liver during cell volume regulatory ion fluxes following exposure of the liver to anisotonic perfusion media. Lowering of the osmolarity in influent perfusate from 305 mOsm/l to 225 mOsm/l (by decreasing influent [NaCl] by 40 mmol/l) led to an inhibition of urea synthesis from NH4Cl (0.5 mmol/l) by about 60% and a decrease of hepatic oxygen uptake by 0.43 +/- 0.03 mumol g-1 min-1 [from 3.09 +/- 0.13 mumol g-1 min-1 to 2.66 +/- 0.12 mumol g-1 min-1 (n = 9)]. The effects on urea synthesis and oxygen uptake were observed throughout hypotonic exposure (225 mOsm/l). They persisted although volume regulatory K+ efflux from the liver was complete within 8 min and were fully reversible upon reexposure to normotonic perfusion media (305 mOsm/l). A 42% inhibition of urea synthesis from NH4Cl (0.5 mmol/l) during hypotonicity was also observed when the perfusion medium was supplemented with glucose (5 mmol/l). Urea synthesis was inhibited by only 10-20% in livers from fed rats, and was even stimulated in those from starved rats when an amino acid mixture (twice the physiological concentration) plus NH4Cl (0.2 mmol/l) was infused. 2. The inhibition of urea synthesis from NH4Cl (0.5 mmol/l) during hypotonicity was accompanied by a threefold increase of citrulline tissue levels, a 50-70% decrease of the tissue contents of glutamate, aspartate, citrate and malate, whereas 2-oxoglutarate, ATP and ornithine tissue levels, and the [3H]inulin extracellular space remained almost unaltered. Further, hypotonic exposure stimulated hepatic glutathione (GSH) release with a time course roughly paralleling volume regulatory K+ efflux. NH4Cl stimulated lactate release from the liver during hypotonic but not during normotonic perfusion. In the absence of NH4Cl, hypotonicity did not significantly affect the lactate/pyruvate ratio in effluent perfusate. With NH4Cl (0.5 mmol/l) present, the lactate/pyruvate ratio increased from 4.3 to 8.2 in hypotonicity, whereas simultaneously the 3-hydroxybutyrate/acetoacetate ratio slightly, but significantly decreased. 3. Addition of lactate (2.1 mmol/l) and pyruvate (0.3 mmol/l) to influent perfusate did not affect urea synthesis in normotonic perfusions, but completely prevented the inhibition of urea synthesis from NH4Cl (0.5 mmol/l) induced by hypotonicity. Restoration of urea production in hypotonic perfusions by addition of lactate and pyruvate was largely abolished in the presence of 2-cyanocinnamate (0.5 mmol/l). Addition of 3-hydroxybutyrate (0.5 mmol/l), but not of acetoacetate (0.5 mmol/l) largely reversed the hypotonicity-induced inhibition of urea synthesis from NH4Cl.(ABSTRACT TRUNCATED AT 400 WORDS) |
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Authors:
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D Hüssinger; F Lang; K Bauers; W Gerok |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of biochemistry / FEBS Volume: 193 ISSN: 0014-2956 ISO Abbreviation: Eur. J. Biochem. Publication Date: 1990 Nov |
Date Detail:
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Created Date: 1991-01-11 Completed Date: 1991-01-11 Revised Date: 2007-07-23 |
Medline Journal Info:
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Nlm Unique ID: 0107600 Medline TA: Eur J Biochem Country: GERMANY |
Other Details:
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Languages: eng Pagination: 891-8 Citation Subset: IM |
Affiliation:
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Medizinische Universitätsklinik Freiburg, Federal Republic of Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Ammonia
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metabolism Ammonium Chloride / metabolism, pharmacology Animals Cinnamates / pharmacology Glucose / metabolism Hypotonic Solutions Kinetics Lactates / metabolism Liver / drug effects, metabolism, physiology* Male Monocarboxylic Acid Transporters Nitrogen / metabolism* Oxygen Consumption Perfusion Pyruvates / metabolism Rats Rats, Inbred Strains Urea / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Cinnamates; 0/Hypotonic Solutions; 0/Lactates; 0/Monocarboxylic Acid Transporters; 0/Pyruvates; 1011-92-3/alpha-cyanocinnamate; 12125-02-9/Ammonium Chloride; 50-99-7/Glucose; 57-13-6/Urea; 7664-41-7/Ammonia; 7727-37-9/Nitrogen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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