cyclic-gmp and isobutyric-acid

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.

Topics: Ammonia; Animals; Arginine; Butyrates; Chromatography, High Pressure Liquid; Corpus Striatum; Cyclic GMP; Diazooxonorleucine; Dose-Response Relationship, Drug; Drug Interactions; Electrochemical Techniques; Glutamine; In Vitro Techniques; Isobutyrates; Male; Microdialysis; Nitric Oxide; Rats; Rats, Sprague-Dawley; Signal Transduction; Time Factors