Document Detail


Interference of L-arginine analogues with L-arginine transport mediated by the y+ carrier hCAT-2B.
MedLine Citation:
PMID:  9701046     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The inducible human cationic amino acid transporter hCAT-2B was expressed in Xenopus laevis oocytes, and this system was used to test the effect of several NO synthase (NOS) inhibitors and/or L-arginine analogues on L-arginine transport by this y+ carrier. L-NG-Methyl-L-arginine (L-NMA), asymmetrical L-NG, NG-dimethyl-L-arginine (L-ADMA), L-N5-(1-iminoethyl)-ornithine (L-NIO), L-NG-nitro-L-arginine (L-NNA), and L-NG-nitro-L-arginine methyl ester (L-NAME) all inhibited the inducible NOS II extracted from RAW 264.7 macrophages induced with bacterial lipopolysaccharide. L-NMA, L-ADMA, and L-NIO also competed with L-arginine for transport by hCAT-2B, whereas L-NNA and L-NAME did not. The two L-arginine analogues, symmetrical NG, NG-dimethyl-L-arginine (L-SDMA) and alpha-amino-delta-isothioureidovaleric acid (AITV), as well as L-lysine, did not block enzymatic activity of NOS II, but did compete for L-arginine transport mediated by hCAT-2B. L-Lysine and L-SDMA were transported efficiently by hCAT-2B and exchanged against intracellular L-arginine, resulting in an L-arginine depletion of the cells. AITV was a much poorer substrate of hCAT-2B and had only little effect on intracellular L-arginine concentrations. These data indicate that substrate recognition differs markedly between the inducible L-arginine transporter hCAT-2B and the inducible NOS II, with different L-arginine analogues having affinity to only one or both of these proteins.
Authors:
E I Closs; F Z Basha; A Habermeier; U Förstermann
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nitric oxide : biology and chemistry / official journal of the Nitric Oxide Society     Volume:  1     ISSN:  1089-8603     ISO Abbreviation:  Nitric Oxide     Publication Date:  1997 Feb 
Date Detail:
Created Date:  1998-09-01     Completed Date:  1998-09-01     Revised Date:  2011-10-27    
Medline Journal Info:
Nlm Unique ID:  9709307     Medline TA:  Nitric Oxide     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  65-73     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Johannes Gutenberg University, Mainz, Germany. closs@mzdmza.zdv.uni-mainz.de
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Transport Systems, Basic
Animals
Arginine / analogs & derivatives*,  metabolism,  pharmacology
Biological Transport
Carrier Proteins / metabolism*
Cell Line
Enzyme Inhibitors
Glucose / metabolism
Glucose Transporter Type 1
Humans
Lysine / pharmacology
Membrane Proteins / metabolism*
Mice
Monosaccharide Transport Proteins / metabolism
Nitric Oxide Synthase / antagonists & inhibitors
Nitric Oxide Synthase Type II
Oocytes / metabolism
Rats
Xenopus laevis
Chemical
Reg. No./Substance:
0/Amino Acid Transport Systems, Basic; 0/Carrier Proteins; 0/Enzyme Inhibitors; 0/Glucose Transporter Type 1; 0/Membrane Proteins; 0/Monosaccharide Transport Proteins; 0/SLC2A1 protein, human; 50-99-7/Glucose; 56-87-1/Lysine; 74-79-3/Arginine; EC 1.14.13.39/NOS2 protein, human; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nos2 protein, mouse; EC 1.14.13.39/Nos2 protein, rat

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