L-glutamine inhibits nitric oxide synthesis in bovine venular endothelial cells.
This study was conducted to test the hypothesis that L-glutamine has differential effects on nitric oxide (NO) synthesis from L-arginine in bovine venular endothelial cells (EC) stimulated by A23187 (a Ca++ ionophore) and receptor-mediated vasodilators (bradykinin and substance P). EC were cultured at 37 degrees C for 24 h in the presence of 0.4 mM L-arginine and 0.0 to 2.0 mM L-glutamine with or without 1 microM A23187, 1 microM bradykinin or 10 microM substance P. The release of nitrite and nitrate by EC was used as an indicator of NO synthesis. A23187, bradykinin or substance P increased NO synthesis from L-arginine by EC in the presence or absence of L-glutamine. The addition of L-glutamine (0.5 and 2 mM) markedly increased intracellular concentrations of L-glutamine, L-glutamate and L-aspartate and decreased NO synthesis by EC in a concentration-dependent manner in the presence or absence of A23187, bradykinin or substance P. L-Glutamine had no effect on L-arginine uptake by EC or on intracellular L-arginine concentration. Neither L-glutamine nor its glutaminase metabolites (ammonia, L-glutamate and L-aspartate) had any effect on endothelial NO synthase activity. Taken together, these results suggest that the inhibition by L-glutamine of NO synthesis from L-arginine is unlikely to result from an effect of L-glutamine on L-arginine transport or NO synthase activity. Although the mechanism involved remains unknown, regulation of the arginine-NO pathway by L-glutamine may have pharmacologic and therapeutic implications in such conditions as inflammation and septic shock by inhibiting NO generation from L-arginine in endothelial cells.
Meininger
C J
CJ
Department of Medical Physiology, Texas A&M University, College Station 77843-1114, USA.
Wu
G
G
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001120:Arginine / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005973:Glutamine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D014699:Venules / Q000378:metabolism
D005973:Glutamine; D009569:Nitric Oxide; D001120:Arginine