Back to Search
Start Over
Glutamine inhibits ammonia-induced accumulation of cGMP in rat striatum limiting arginine supply for NO synthesis.
- Source :
-
Neurobiology of disease [Neurobiol Dis] 2009 Jul; Vol. 35 (1), pp. 75-81. Date of Electronic Publication: 2009 Apr 18. - Publication Year :
- 2009
-
Abstract
- Brain L-glutamine (Gln) accumulation and increased activity of the NO/cGMP pathway are immediate consequences of acute exposure to ammonia. This study tested whether excess Gln may influence NO and/or cGMP synthesis. Intrastriatal administration of the glutaminase inhibitor 6-diazo-5-oxo-L-norleucine or the system A-specific Gln uptake inhibitor methylaminoisobutyrate increased microdialysate Gln concentration and reduced basal and ammonia-induced NO and cGMP accumulation. Gln applied in vivo (via microdialysis) or in vitro (to rat brain cortical slices) reduced NO and cGMP accumulation in the presence and/or absence of ammonia, but not cGMP synthesis induced by the NO donor sodium nitroprusside. Attenuation of cGMP synthesis by Gln was prevented by administration of L-arginine (Arg). The L-arginine co-substrates of y(+)LAT2 transport system, L-leucine and cyclo-leucine, mimicked the effect of exogenous Gln, suggesting that Gln limits Arg supply for NO synthesis by interfering with y+LAT2-mediated Arg uptake across the cell membrane.
- Subjects :
- Animals
Butyrates pharmacology
Chromatography, High Pressure Liquid methods
Corpus Striatum metabolism
Diazooxonorleucine pharmacology
Dose-Response Relationship, Drug
Drug Interactions
Electrochemical Techniques methods
Glutamine metabolism
In Vitro Techniques
Isobutyrates
Male
Microdialysis methods
Rats
Rats, Sprague-Dawley
Time Factors
Ammonia pharmacology
Arginine metabolism
Corpus Striatum drug effects
Cyclic GMP metabolism
Glutamine pharmacology
Nitric Oxide metabolism
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-953X
- Volume :
- 35
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Neurobiology of disease
- Publication Type :
- Academic Journal
- Accession number :
- 19379813
- Full Text :
- https://doi.org/10.1016/j.nbd.2009.04.004