| Further observations on the uptake and effects of phosphonates in perfused rat liver studied by (31)P-NMR. | |
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MedLine Citation:
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PMID: 10484816 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We examined the route of uptake of 2-aminoethylphosphonate (NEthPo) and of phenylphosphonate (PhePo; 10 mM each) in perfused liver by (31)P-NMR. Uptake of NEthPo was concentrative. The rate of uptake was reduced to 21 +/- 2% (n = 3; all percentages refer to control rates) by substituting choline for Na(+), and to 21 +/- 4% (n = 3), 32 +/- 6% (n = 5) and 70 +/- 5% (n = 3) by replacing Cl(-) by gluconate, SO(4)(2-) or NO(3)(-), respectively. Taurine (20 mM) reduced NEthPo uptake to 38 +/- 6% (n = 3). The data are consistent with uptake of NEthPo by the Na(+)-coupled Cl(-)-dependent beta-amino acid transporter. A small fraction of NEthPo was incorporated into phospholipid. PhePo uptake evolved over 1 h towards levels of the membrane-permeant volume marker dimethyl methylphosphonate. Uptake depended on H(+), and was inhibited by 4, 4'-diisothiocyanato-stilbene-2,2'-disulphonic acid (100 microM), bumetanide and furosemide (1 mM each) and alpha-cyano-4-OH-cinnamic acid (5 mM) to 31 +/- 4% (n = 4), 28 +/- 4% (n = 4), 27 +/- 5% (n = 6) and 40 +/- 7% (n = 4), respectively. These characteristics of PhePo uptake are reminiscent of H(+)-coupled monocarboxylate transport. The monocarboxylates, lactate and acetate (20 mM), and the substrate analogue, phenylalanine (20 mM), were not inhibitory, while benzoic acid (20 mM) slightly inhibited (to 82 +/- 5%; n = 4) PhePo uptake. The tested phosphonates (10 mM) did not significantly affect hepatic extraction of [(3)H]-cholate or [(3)H]-taurocholate (25 microM each; 1:3 bile salt:albumin). The monocarboxylate analogue, PhePo (10 mM), did not significantly interfere with disposal of lactate (0.3-5 mM). |
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Authors:
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K Bruynseels; P Van Hecke; F Vanstapel |
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Publication Detail:
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Type: Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: NMR in biomedicine Volume: 12 ISSN: 0952-3480 ISO Abbreviation: NMR Biomed Publication Date: 1999 Aug |
Date Detail:
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Created Date: 1999-10-20 Completed Date: 1999-10-20 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8915233 Medline TA: NMR Biomed Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 275-85 Citation Subset: IM |
Copyright Information:
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Copyright 1999 John Wiley & Sons, Ltd. |
Affiliation:
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Biomedical NMR Unit, Department of Radiology, Faculteit Geneeskunde, Katholieke Universiteit Leuven, Herestraat 49, B-3000, Leuven, Belgium. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aminoethylphosphonic Acid
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antagonists & inhibitors,
pharmacokinetics*,
pharmacology* Animals Bile Acids and Salts / metabolism Biological Transport Carrier Proteins / metabolism Cinnamates / metabolism Hydrogen-Ion Concentration Kinetics Lactic Acid / metabolism Liver / drug effects*, metabolism* Male Membrane Glycoproteins / metabolism Membrane Transport Proteins* Monocarboxylic Acid Transporters Nuclear Magnetic Resonance, Biomolecular Organophosphorus Compounds / antagonists & inhibitors, pharmacokinetics*, pharmacology* Perfusion Rats Rats, Wistar Reproducibility of Results |
| Chemical | |
Reg. No./Substance:
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0/Bile Acids and Salts; 0/Carrier Proteins; 0/Cinnamates; 0/Membrane Glycoproteins; 0/Membrane Transport Proteins; 0/Monocarboxylic Acid Transporters; 0/Organophosphorus Compounds; 1011-92-3/alpha-cyanocinnamate; 148686-53-7/taurine transporter; 1571-33-1/phenylphosphonic acid; 2041-14-7/Aminoethylphosphonic Acid; 50-21-5/Lactic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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