Document Detail


y+ LAT-1 mediates transport of the potent and selective iNOS inhibitor, GW274150, in control J774 macrophages.
MedLine Citation:
PMID:  16699825     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study has characterised the transport mechanism(s) for the novel and selective inhibitor of inducible nitric oxide synthase (iNOS), GW274150, in murine macrophage J774 cells. Transport of GW274150 was saturable (K(m) = 0.24 +/- 0.01 mM and V(max) of 8.5 +/- 0.12 pmol.microg protein(-1) min(-1)), pH-insensitive and largely Na(+)-independent. Transport was also susceptible to trans-stimulation and was significantly inhibited by a 10-fold excess of L-arginine, L-lysine, L-leucine, L-methionine, L-glutamine and 6-diazo-5-oxo-L-norleucine but not by other amino acids or by N-ethylmaleimide. More importantly, the inhibitions caused by the neutral amino acids were critically dependent on Na(+). These results strongly implicate system y(+)L in the transport of GW274150. Northern blot analysis confirmed this by revealing the presence of transcripts for y(+)LAT-1 but not y(+)LAT-2. Thus, taken together, our data show for the first time that J774 macrophages express y(+)LAT-1 transporters and that these carriers mediate transport of GW2741500 at least in these cells.
Authors:
A R Baydoun; J Bertran; S Thakur; J Dawson; M Palacín; R G Knowles
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-05-15
Journal Detail:
Title:  Amino acids     Volume:  31     ISSN:  0939-4451     ISO Abbreviation:  Amino Acids     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-14     Completed Date:  2007-10-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9200312     Medline TA:  Amino Acids     Country:  Austria    
Other Details:
Languages:  eng     Pagination:  101-9     Citation Subset:  IM    
Affiliation:
School of Life Sciences, University of Hertfordshire, Hatfield, UK. a.baydoun@herts.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Transport System y+L / genetics,  physiology*
Animals
Biological Transport
Blotting, Northern
Cell Line
Enzyme Inhibitors / pharmacokinetics*
Ethylmaleimide / pharmacology
Hydrogen-Ion Concentration
Macrophages / drug effects*,  enzymology,  metabolism
Mice
Nitric Oxide Synthase Type II / antagonists & inhibitors*
Sodium / metabolism
Sulfides / pharmacokinetics*
Chemical
Reg. No./Substance:
0/Amino Acid Transport System y+L; 0/Enzyme Inhibitors; 0/GW 274150; 0/Sulfides; 128-53-0/Ethylmaleimide; 7440-23-5/Sodium; EC 1.14.13.39/Nitric Oxide Synthase Type II

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