Glutamine inhibits ammonia-induced accumulation of cGMP in rat striatum limiting arginine supply for NO synthesis

Autor: Wojciech Hilgier, Inez Fręśko, Emilia Klemenska, Andrzej Beręsewicz, Simo S. Oja, Pirjo Saransaari, Jan Albrecht, Magdalena Zielińska
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Zdroj: Neurobiology of Disease, Vol 35, Iss 1, Pp 75-81 (2009)
Druh dokumentu: article
ISSN: 1095-953X
DOI: 10.1016/j.nbd.2009.04.004
Popis: 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.
Databáze: Directory of Open Access Journals
Externí odkaz: